Hb Bois Guillaume alpha65(E14)Ala->Val CONTACT External HEMATOLOGY Mild anemia in the proband; others were normal ELECTROPHORESIS Partial separation of Hb X and Hb A by IEF CHROMATOGRAPHY Partial separation of Hb X and Hb A by cation exchange HPLC; no separation of alpha chains by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of AE-alphaA+alphaX chains; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCG->GTG at codon 65; alpha2 or alpha1 FUNCTION STUDIES Not reported; oxygen binding properties of red cells normal STABILITY Mildly unstable OCCURRENCE Found in members of a French family OTHER INFORMATION Quantity in the heterozygote ~20% REFERENCES 1. Wajcman, H., Blouquit, Y., Lahary, A., Soummer, A.M., Groff, P., Bardakdjian, J., Prehu, C., Riou, J., Godard, C., and Galacteros, F.: Hemoglobin, 19:281, 1995. Hb Gouda alpha72(EF1)His->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation by standard techniques; Hb X focuses ahead of Hb A in IEF CHROMATOGRAPHY Partial separation of Hb X and Hb A by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A CAC->CAA mutation at codon 72 of the alpha2 gene FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 54-year-old Dutch female and her four children OTHER INFORMATION Quantity in the heterozygote not listed REFERENCES 1. Giordano, P.C., Harteveld, C.L., Kok, P.J.M.J., Geenen, A., Batelaan, D., Amons, R., and Bernini, L.F.: Hemoglobin, 20:21, 1996. Hb Fuchu-I alpha72(EF1)His->Tyr CONTACT External; no contact with heme or other chain HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X focuses ahead of Hb A by IEF CHROMATOGRAPHY Hb X and Hb A separate by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->TAC at codon 72; alpha2 or alpha1 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 27-year-old Japanese female OTHER INFORMATION Quantity in the heterozygote ~22% REFERENCES 1. Harano, T., Harano, K., Uehara, S., and Matsushita, K.: Hemoglobin, 19:389, 1995. Hb Fuchu-II alpha97(G4)Asn->His CONTACT Central cavity at the alpha1beta1 region HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation by IEF CHROMATOGRAPHY Hb X elutes in front of Hb A in cation exchange HPLC; alphaX elutes later than alphaA from a CM-cellulose column STRUCTURE STUDIES Digestion of alphaX chain with trypsin; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->CAC at codon 97; alpha2 or alpha1 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a healthy Japanese male OTHER INFORMATION The alphaX was ~25% of total alpha REFERENCES 1. Harano, T., Harano, K., Uehara, S., and Matsushita, K.: Hemoglobin, 19:389, 1995. Hb Mosella alpha111(G18)Ala->Thr CONTACT alpha1beta1 contact HEMATOLOGY Normal in heterozygotes ELECTROPHORESIS Hb X focuses between Hb A and Hb A1c on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of alphaX+alphaA chains; separation of pep-tides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->ACC; alpha2 or alpha1 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Observed in a 35-year-old female from Luxembourg and in one of her daughters OTHER INFORMATION Quantity of Hb X ~20% REFERENCES 1. Wajcman, H., Blouquit, Y., Lahary, A., Soummer, A.M., Groff, P., Bardakdjian, J., Prehu, C., Riou, J., Godard, C., and Galacteros, F.: Hemoglobin, 19:281, 1995. Hb Saclay alpha133(H16)Ser->Asn CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation from Hb A except by IEF CHROMATOGRAPHY Not reported; partial separation of alphaX and alphaA chains by perfusion chromatography on a Poros RI column STRUCTURE STUDIES Tryptic digestion of AE-alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; electrospray analysis DNA ANALYSES Not reported; presumed mutation AGC->AAC at codon 133; alpha2 or alpha1 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in an Algerian-Alsatian female OTHER INFORMATION Abnormal Hb was 20% of total Hb REFERENCES 1. Wajeman, H., Prome, D., Riou, J., Mathis, M., Godart, C., Hurtrel, D., Prehu, C., Bardakkjian, J., Bridey, F., and Galacteros, F.: Abstract 48, Nouv. Rev. Fr. d'Hematol., 38:27, 1996. Hb Nakano beta8(A5)Lys->Met CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on IEF CHROMATOGRAPHY Hb X and Hb A separate on anion exchange HPLC columns; the betaX chain elutes ahead of betaA from a CM-cellulose column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->ATG at codon 8 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 46-year-old Japanese woman OTHER INFORMATION Quantity in the heterozygote 45.3% REFERENCES 1. Harano, K., Harano, T., Koide, G., and Akimaru, S.: Hemoglobin, 19:397, 1995. Hb Iraq-Halabja beta10(A7)Ala->Val CONTACT External HEMATOLOGY No data for the simple heterozygote ELECTROPHORESIS No separation CHROMATOGRAPHY No separation STRUCTURE STUDIES Not reported DNA ANALYSES A GCC->GTC mutation at codon 10 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in members of an Iraqi family OTHER INFORMATION Occurred together with beta-thal (IVS-II-1, C->T) REFERENCES 1. Beris, Ph., Darbellay, R., Frutiger, A., and Hochstrasser, D.: Blood, 88:642a (Suppl. 1), 1995. Hb Uxbridge beta20(B2)Val->Gly CONTACT External HEMATOLOGY Normal in the heterozygote (PCV 0.42 l/l) ELECTROPHORESIS Hb X moves slower than Hb A on IEF; no separation by cellulose acetate electrophoresis CHROMATOGRAPHY The betaX and betaA chains separation by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; location of the Val->Gly replacement determined by collision induced dissociation spectral analysis DNA ANALYSES Not reported; presumed mutation GTG->GGG at codon 20 FUNCTION STUDIES Mildly increased oxygen affinity; Bohr effect and heme-heme interaction are normal STABILITY Normal OCCURRENCE Found in an English newborn and her mother OTHER INFORMATION Quantity in the adult heterozygote ~40% REFERENCES 1. Wajcman, H., Prome, D., Kister, J., Davies, S.C., Galacteros, F., and Henthorn, J.S.: Hemoglobin, 20:339, 1996. Hb Aubenas beta26(B8)Glu->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH CHROMATOGRAPHY Hb X and Hb A readily separate in cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by HPLC; amino acid analysis; mass spectrometry DNA ANALYSES A GAG->GGG mutation at codon 26 FUNCTION STUDIES Normal STABILITY Mildly unstable OCCURRENCE Found in a French family OTHER INFORMATION Quantity in the heterozygote 39%; in vitro chain synthesis alpha/(betaA+betaX) 0.96; no thalassemic features REFERENCES 1. Lacan, P., Francina, A., Prome, Galacteros, F., and Wajcman, H.: Hemoglobin, 20:113, 1996. Hb Karlsruhe beta28(B10)Leu->Met CONTACT Internal HEMATOLOGY No details provided; methemoglobinemia ELECTROPHORESIS Hb X moves like Hb F at alkaline pH; not detectable by IEF CHROMATOGRAPHY No separation by cation exchange HPLC STRUCTURE STUDIES Not reported DNA ANALYSES ACTG->ATG mutation at codon 28 FUNCTION STUDIES MetHb level ~8% STABILITY Unstable OCCURRENCE Found in several members of a family from Southern Germany OTHER INFORMATION None REFERENCES 1. Seelig, H.P.: Personal communication, 1995. Hb Hinwil beta38(C4)Thr->Asn CONTACT Heme contact HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.45-0.50 l/l) ELECTROPHORESIS Hb X and Hb A partially separate by IEF CHROMATOGRAPHY No separation by cation exchange HPLC; betaX separates from betaA and alpha by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES The tryptic betaXT-4 peptide was isolated and sequenced DNA ANALYSES An ACC->AAC mutation at codon 38 FUNCTION STUDIES Increased oxygen affinity; reduced cooperativity STABILITY Normal OCCURRENCE Found in a Swiss female and her two daughters OTHER INFORMATION betaX = 44% of betaA+betaX REFERENCES 1. Frischknecht, H., Ventruto, M., Hess, D., Hunziker, P., Rosatelli, M.C., Cao, A., Breitenstein, U., Fehr, J., and Tuchschmid.: Hemoglobin, 20:31, 1996. Hb J-Europa beta62(E6)Ala->Asp CONTACT External HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.50 l/l) ELECTROPHORESIS Hb JX and Hb A separate at alkaline pH and by IEF CHROMATOGRAPHY Hb JX can be isolated by cation or anion exchange chroma-tography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCT->GAT at codon 62 FUNCTION STUDIES Normal oxygen binding STABILITY Normal OCCURRENCE Found in a few members of an Italian family OTHER INFORMATION Quantity in the heterozygote 43% REFERENCES 1. Kiger, L., Groff, P., Kalmes, G., Kister, J., Prome, D., Galacteros, F., and Wajcman, H.: Hemoglobin, 20:135, 1996. Hb Costa Rica beta77(EF1)His->Arg CONTACT External HEMATOLOGY Normal in the carrier ELECTROPHORESIS Hb X can be separated from Hb A at alkaline pH (moves like Hb S) CHROMATOGRAPHY Excellent separation by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of isolated AE-betaX chain; separation of tryptic peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES See below FUNCTION STUDIES Not determined STABILITY Stable OCCURRENCE Found in a Costa Rican female but not in her immediate relatives OTHER INFORMATION The expected CAC->CGC mutation at codon 77 could not be observed in genomic DNA or in cDNA. However, a small amount of beta-Costa Rica cDNA (or mRNA) could be detected by ASO and dot-blot analysis with 32P-labeled probes. The same experiments were negative for genomic DNA. These results, the low level of the stable Hb Costa Rica (5-6%), and the unequal distribution of the variant over the red cells are explained by assuming a somatic mosaicism as the genetic basis of the occurrence of this variant. REFERENCES 1. Rodriguez Romero, W.E., Castillo, M., Chaves, M.A., Saenz, G.F., Gu, L-H., Wilson, J.B., Baysal, E., Smetanina, N.S., Leonova, J.Ye., and Huisman, T.H.J.: Hum. Genet., 97:829, 1996. 2. Smetanina, N.S., Gu, L-H., Rodriguez Romero, W.E., Howard, E.F., and Huisman, T.H.J.: Hemoglobin, 20:199, 1996. Hb Tsurumai beta82(EF6)Lys->Gln CONTACT 2,3-DPG binding site HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.56-0.58 l/l) ELECTROPHORESIS Hb X focuses ahead of Hb A in IEF CHROMATOGRAPHY Hb X and Hb A readily separate by anion or cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->CAG at codon 82 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a 46-year-old Japanese male and his son OTHER INFORMATION Quantity in the heterozygote ~49% REFERENCES 1. Ohba, Y., Yamada, H., Takamatsu, S., and Imai, K.: Hemoglobin, 20:141, 1996. Hb Debrousse beta96(FG3)Leu->Pro CONTACT Heme contact HEMATOLOGY Chronic hemolytic anemia; hemoglobinuria; reticulocytosis ELECTROPHORESIS Not easily observed by cellulose acetate electrophoresis and IEF CHROMATOGRAPHY The betaX chain separates from betaA and alpha by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES A CTG->CCG mutation at codon 96 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect STABILITY Decreased stability OCCURRENCE Found in a 6-year-old of Italian/French descent; parents are normal OTHER INFORMATION betaX = 35% of betaA+betaX REFERENCES 1. Lacan, P., Kister, J., Francina, A., Souillet, G., Galacteros, F., Delaunay, J., and Wajcman, H.: Am. J. Hematol., 51:276, 1996. Hb Alzette beta104(G6)Arg->Lys CONTACT Central cavity HEMATOLOGY Normal in the heterozygote; mild microcytosis ELECTROPHORESIS No separation by routine methodology CHROMATOGRAPHY The variant was found by cation exchange HPLC; no other information available STRUCTURE STUDIES Electrospray mass spectrometry; tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGG->AAG at codon 104 FUNCTION STUDIES Normal oxygen affinity STABILITY Not reported OCCURRENCE Found in a teenager from Luxembourg OTHER INFORMATION Present for 35% in the heterozygote REFERENCES 1. Kister, J., Papassotiriou, I., Groff, P., Kalmes, G., Prome, D., and Wajcman, H.: Abstract 46, Nouv. Rev. Fr. d'Hematol., 38:26, 1996. Hb F-Macedonia-I Agamma2(NA2)His->Gln ELECTROPHORESIS Hb FX was detected by PAGE IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION AgammaX = 15%; Ggamma = 70.8%; Agamma = 14.2% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis identified a His-> Glu or Gln change DNA ANALYSES A CAT->CAG (His->Gln) mutation at codon 2 NOTES Found in a healthy Macedonian baby; Hb FX 15% of total Hb F REFERENCES 1. Plaseska, D., Cepreganova-Krstik, B., Momirovska, A., and Efremov, G.D.: Hemoglobin, 18:241, 1994. Hb F-Texas-I Agamma5(A2)Glu->Lys ELECTROPHORESIS Hb FX moves slower than Hb C at alkaline pH IEF About the same CHROMATOGRAPHY Hb FX can be isolated by cation and anion exchange HPLC CHAIN SEPARATION No data reported STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->AAG at codon 5 NOTES Found in several Black babies; quantity in heterozygotes ~12%; the gamma-Texas-I chain is considerably acetylated (three time more than the normal gamma chain) REFERENCES 1. Jenkins, G.C., Beale, D., Black, A.J., Huntsman, G.R., and Lehmann, H.: Br. J. Haematol., 13:252, 1967. 2. Ahern, E.J., Wiltshire, B.G., and Lehmann, H.; Biochim. Biophys. Acta, 271:61, 1972. 3. Keitt, A.S. and Jones, R.T.: Am. J. Hematol., 28:47, 1988. Hb F-Kotobuku Agamma6(A3)Glu->Gly ALSO KNOWN AS Izumi ELECTROPHORESIS Hb FX moves slightly slower than Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes between Hb A2 and Hb A on a DEAE-cellulose column CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GGG at codon 6 NOTES Found in a Japanese baby; quantity in the heterozygote not reported REFERENCES 1. Yoshinaka, H., Ohba, Y., Hattori, Y., Matsuoka, M., Miyaji, T., and Fuyuno, K.: Hemoglobin, 6:37, 1982. 2. Wada, Y., Hayashi, A., Masanori, I., Katakuse, T., Ichihara, H., Nakabushi, T., Matsuo, T., Sakurai, T., and Matsuda, H.: Biochim. Biophys. Acta, 749:244, 1983. Hb F-Pordenone Agamma6(A3)Glu->Gln ELECTROPHORESIS Hb FX moves slightly slower than Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes between Hb A2 and Hb A on a DEAE-cellulose column CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->CAG at codon 6 NOTES Found in an Italian newborn; Hb FX 5.7 of total Hb and 8.6% of total Hb F REFERENCES 1. Nakatsuji, T., Webber, B., Lam, H., Wilson, J.B., Huisman, T.H.J., Sciarratta, G.V., Sansone, G., and Molaro, G.L.: Hemoglobin, 6:397, 1982. Hb F-Calluna Agamma12(A9)Thr->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes between Hb A2 and Hb A on a DEAE-cellulose column CHAIN SEPARATION AgammaX = 10.7%; Ggamma = 71.5%; AgammaT = 17.8% STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation ACA->AGA at codon 12 NOTES Found in a Caucasian baby; Hb FX 8.7% of total Hb or 10.8% of total Hb F; baby was also heterozygous for the AgammaT chain REFERENCES 1. Nakatsuji, T., Lam, H., and Huisman, T.H.J.: Hemoglobin, 7:563, 1983. Hb F-Kuala Lumpur Agamma22(B4)Asp->Gly ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX and Hb A cannot be separated by DEAE-Sephadex chromatography CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAT->GGT at codon 22 NOTES Found in a Few Indian newborn babies; Hb FX 11% of total Hb REFERENCES 1. Lie-Injo, L.E., Wiltshire, B.G., and Lehmann, H.: Biochim. Biophys. Acta, 322:224, 1973. Hb F-Pendergrass Agamma36(C2)Pro->Arg ELECTROPHORESIS Hb FX moves about like Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX separates from Hb A and Hb F by DEAE-cellulose chromatography CHAIN SEPARATION No data reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCA->CGA at codon 36 NOTES Found in a Caucasian newborn; Hb FX 6.7% of total Hb or 8.5% of total Hb F REFERENCES 1. Chen, S.S., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 9:73, 1985. Hb F-Cobb Agamma37(C3)Trp->Gly ELECTROPHORESIS Hb FX moves slower than Hb F at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX can be separated from Hb A and Hb F by DEAE-cellulose chromatography CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TGG->GGG at codon 37 NOTES Found in a Caucasian baby; no quantitative data at birth REFERENCES 1. Chen, S.S., Webber, B.B., Kutlar, A., Wilson, J.B., and Huisman, T.H.J.: 9:617, 1985. Hb F-Bonaire-GA Agamma39(C5)Gln->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX readily separates from Hb F and Hb A by DEAE-cellulose chromatography CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gamma-FX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAG->CGG at codon 39 NOTES Found in a Caucasian-Vietnamese baby; Hb FX 8.3% of total Hb or 9.8% of total Hb F REFERENCES 1. Nakatsuji, T., Headlee, M., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 6:599, 1982. Hb F-Woodstock Agamma40(C6)Arg->Lys ELECTROPHORESIS Not determined IEF Hb FX focused close to Hb F CHROMATOGRAPHY Hb FX elutes slightly later than Hb F by cation exchange HPLC CHAIN SEPARATION No quantitative data STRUCTURE STUDIES Not presented DNA ANALYSES An AGG->AAG mutation at codon 40 NOTES Found in a Black newborn REFERENCES 1. Huisman, T.H.J., Kutlar, F., and Gu, L-H.; Hemoglobin, 15:349, 1991. Hb F-Beech Island Agamma53(D4)Ala->Asp ELECTROPHORESIS Hb FX moves slightly faster than Hb A at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes together with minor Hb F1 in DEAE-cellulose chromatography CHAIN SEPARATION AgammaX = 12%; Ggamma = 74.1%; Agamma = 13.9% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 53 NOTES Found in a few Caucasian and Black babies in the SE-USA; quantity of Hb FX estimated at 15-16% REFERENCES 1. Chen, S.S., Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 9: 525, 1985. Hb F-Jamaica Agamma61(E5)Lys->Glu ELECTROPHORESIS Hb FX moves much faster than Hb A at alkaline pH; slightly slower than Hb Bart's (or gamma4) IEF Not reported CHROMATOGRAPHY Hb FX was isolated by DEAE-Sephadex and Bio-Rex 70 chromatography CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; se-quencing DNA ANALYSES Not reported; presumed mutation AAG->GAG at codon 61 NOTES Found in a Jamaican newborn of mixed ethnic origin; Hb FX 11-15% of total Hb F REFERENCES 1. Ahern, E.J., Jones, R.T., Brimhall, B., and Gray, R.H.: Br. J. Haematol., 18:369, 1970. Hb F-Iwata Agamma72(E16)Gly->Arg ELECTROPHORESIS Hb FX moves slightly slower than Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes between Hb A2 and Hb A from a DEAE-cellulose column CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGA->CGA at codon 72 NOTES Found in a few Japanese newborn babies; quantity in the heterozygote ~11% of total Hb F REFERENCES 1. Fuyuno, K., Torigoe, T., Ohba, Y., Matsuoka, M., and Miyaji, T.: Hemoglobin, 5: 139, 1981. Hb F-Xin-Su Agamma73(E17)Asp->His ELECTROPHORESIS Hb FX moves between Hb A and Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX can readily be isolated by DEAE-cellulose chromatography CHAIN SEPARATION AgammaX = 12.7%; AgammaT = 14.9%; Ggamma = 72.4% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->CAT at codon 73 NOTES Found in a Chinese baby of the Han nationality; the baby was also heterozygous for the AgammaT chain REFERENCES 1. Ma, M., Hu, H., Kutlar, F., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 11:473, 1987. Hb F-Sardinia (AgammaT) Agamma75(E19)Ile->Thr ELECTROPHORESIS No separation reported IEF (Nearly) no separation CHROMATOGRAPHY No separation CHAIN SEPARATION AgammaT = ~15%; Ggamma = ~70%; AgammaI = ~15% STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES An ATA->ACA mutation at codon 75 NOTES Found at high frequencies in nearly all populations; quantity in heterozygotes ~15% of total Hb F REFERENCES 1. Grifoni, V., Kamuzora, H., Lehmann, H., and Charlesworth, D.: Acta Haematol., 53:347, 1975. 2. Huisman, T.H.J., Schroeder, W.A., Reese, A., Wilson, J.B., Lam, H., Shelton, J.R., Shelton, J.B., and Baker, S.: Pediatr. Res., 11:1102, 1977. 3. Huisman, T.H.J., Kutlar, F., Nakatsuji, T., Bruce-Tagoe, A., Kilinc, Y., Cauchi, M.N., and Romero Garcia, C.: Hum. Genet., 71:127, 1985. Hb F-Dammam Agamma79(EF3)Asp->Asn ELECTROPHORESIS Hb FX moves between Hb S and Hb C IEF Not reported CHROMATOGRAPHY Hb FX elutes between Hb A2 and Hb A on DEAE-cellulose; no separation from Hb A in cation exchange HPLC CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 79 NOTES Found in an Arabian newborn who is also heterozygous for the AgammaT chain; Hb FX 6.9% of total Hb or 13.1% of total Hb F REFERENCES 1. Al-Awamy, B.H., Niazi, G.A., Al-Mouzan, M.I., Wilson, J.B., Chen, S.S., Webber, B.B., and Huisman, T.H.J.: 9:171, 1985. Hb F-Victoria Jubilee Agamma80(EF4)Asp->Tyr ELECTROPHORESIS Hb FX moves slightly slower than Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes between Hb A and Hb F from a DEAE-cellulose column CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->TAT at codon 80 NOTES Found in a Black newborn; quantity in the heterozygote 7% of total Hb F REFERENCES 1. Ahern, A., Holder, W., Ahern, V., Serjeant, G.R., Serjeant, B.E., Forbes, M., Brimhall, B., and Jones, R.T.: Biochim. Biophys. Acta, 393:188, 1975. Hb F-Dickinson Agamma97(FG4)His->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by cation exchange HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAT->CGT at codon 97 NOTES Found in a few babies of various ethnic backgrounds REFERENCES 1. Schneider, R.G., Haggard, M.E., Gustavson, L.P., Brimhall, B., and Jones, R.T.: Br. J. Haematol., 28:515, 1975. Hb F-Hull Agamma121(GH4)Glu->Lys ELECTROPHORESIS Hb FX moves slower than Hb C IEF The same CHROMATOGRAPHY Hb FX elutes first from a DEAE-cellulose column CHAIN SEPARATION AgammaX = 11.5%; Ggamma = 72.5%; Agamma = 16% STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by fingerprinting; cation exchange HPLC; amino acid analysis DNA ANALYSES A GAA->AAA mutation at codon 121 NOTES Found in babies of English descent; quantity in heterozygotes 7-9% of total Hb F REFERENCES 1. Sacker, L.S., Beale, D., Black, A.J., Huntsman, R.G., Lehmann, H., and Lorkin, P.A.: Br. Med. J., 3:531, 1967. 2. Ahern, E.J., Ahern, V., Wiltshire, B.G., and Lehmann, H.: Biochim. Biophys. Acta, 303:242, 1973. 3. Nakatsuji, T., Burnley, M.S., and Huisman, T.H.J.: Blood, 66:803, 1985. Hb F-Baskent Agamma128(H6)Ala->Thr ELECTROPHORESIS No separation IEF No separation CHROMATOGRAPHY No separation CHAIN SEPARATION AgammaX = 16.3%; Ggamma = 64.6%; Agamma = 19.1% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCT->ACT at codon 128 NOTES Found in a Turkish baby REFERENCES 1. Altay, C., Gurgey, A., Wilson, J.B., Hu, H., Webber, B.B., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 12:87, 1988. Hb F-Jiangsu Agamma134(H12)Val->Met ELECTROPHORESIS Not reported IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION AgammaX = 14.7%; Ggamma = 64.2%; Agamma = 21.1% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTG->AGT at codon 134 NOTES Found in a Chinese newborn REFERENCES 1. Plaseska, D., Kutlar, F., Wilson, J.B., Webber, B.B., Zeng, Y-T., and Huisman, T.H.J.: Hemoglobin, 14:177, 1990. Hb Chongqing alpha2(NA2)Leu->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Starch gel and cellulose acetate electrophoresis at alkaline pH showed a slowly-moving band corresponding to Hb G CHROMATOGRAPHY Hb X can be separated from Hb A by cation and anion exchange chromatography STRUCTURE STUDIES Hb X was identified by fingerprinting; peptide alphaT-1 had disappeared and two new peptide spots were observed because of the Leu->Arg substitution at position 2 of the alpha chain DNA ANALYSES Not reported; presumed mutation CTG->CGG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Unstable OCCURRENCE In a Chinese family OTHER INFORMATION About 9% in heterozygotes REFERENCES 1. Zeng, Y-T., Huang, S-Z., Qiu, X-K., Cheng, G-C., Ren, Z-R., Jin, Q-C., Chen, C-Y., Jiao, C-T., Tang, Z-G., Liu, R-H., Bao, X-H., Zeng, L-Z., Duan, Y-Q., and Zhang, G-Y.: Hemoglobin, 8:569, 1984. Hb J-Toronto alpha5(A3)Ala->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Separates as a fast-moving Hb J from Hb A at alkaline pH CHROMATOGRAPHY Hb X can be separated from Hb A by cation and anion exchange chromatography STRUCTURE STUDIES Hb X was identified by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE In two English families OTHER INFORMATION Quantity in heterozygotes 25-35% REFERENCES 1. Crookston, J.H., Beale, D., Irvine, D., and Lehmann, H.: Nature, 208:1059, 1965. 2. Vella, F., Hill, J.R., Wiltshire, B., and Lehmann, H.: Clin. Biochem., 4:137, 1971. Hb Karachi alpha5(A3)Ala->Pro CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A in cellulose acetate at pH 8.4 CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->CCC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE In a healthy Pakistani male OTHER INFORMATION None REFERENCES 1. Ahmad, A., Naqvi, S., Ehsanullah, S., and Zaidi, Z.H.: J. Pakistani Med. Assoc., 36:206, 1986. Hb Sawara alpha6(A4)Asp->Ala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly slower than Hb F in starch gel electrophoresis at pH 8.6 CHROMATOGRAPHY Hb X elutes as a shoulder in front of Hb A on a DEAE-Sephadex column STRUCTURE STUDIES tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GCC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; normal Bohr effect STABILITY Normal OCCURRENCE In three members of a Japanese family OTHER INFORMATION Quantity in heterozygotes 17% REFERENCES 1. Sumida, I., Ohta, Y., Imamura, T., and Yanase, T.: Biochim. Biophys. Acta, 322: 23, 1973. 2. Sumida, I., Jpn. J. Hum. Genet., 19:343, 1975. 3. Sasaki, J., Imamura, T., Sumida, T., Yanase, T., and Ohya, M.: Biochim. Biophys. Acta, 495:183, 1977. Hb Dunn alpha6(A4)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves like Hb F on cellulose acetate (pH 8.4); it moves between Hb A and Hb S on citrate agar (pH 6.0) CHROMATOGRAPHY Hb X separates from Hb A by DEAE-Sephadex or DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; carboxypeptidase; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; Bohr and 2,3-DPG effects normal STABILITY Normal OCCURRENCE In Black, Indian, and Moroccan families OTHER INFORMATION Quantity in heterozygotes 11.6% REFERENCES 1. Jue, D.L., Johnson, M.H., Patchen, L.C., and Moo-Penn, W.F., Hemoglobin, 3: 137, 1979. 2. Charache, S., Brimhall, B., and Zaatari, G., Am. J. Hematol., 9:151, 1980. 3. Nakatsuji, T., Webber, B.B., Johnson, S.E.N., and Huisman, T.H.J.: Hemoglobin, 7:597, 1983. 4. Baklouti, F., Francina, A., Dorleac, E., Baudin-Chich, V., Gombaud-Saintonge, G., Plauchu, H., Wajcman, H., Delaunay, J., and Godet, J.: Am. J. Hematol., 27: 253, 1988. Hb Ferndown alpha6(A4)Asp->Val CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb S but very close to Hb A at alkaline pH (8.9); it separates from Hb A on citrate agar at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GTC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; Bohr and cooperativity effects normal STABILITY Normal OCCURRENCE Found in a 40-year-old British woman OTHER INFORMATION Quantity in the heterozygote 8% REFERENCES 1. Lee-Potter, J.P., Deacon-Smith, R.A., Lehmann, H., and Robb, L.: FEBS Lett., 126:117, 1981. Hb Woodville alpha6(A4)Asp->Tyr CONTACT External; partly buried HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Electrophoresis at pH 9.2 gave a slow-moving component migrating close to the position of Hb F; this band did not separate from Hb A on citrate agar electrophoresis CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly increased oxygen affinity STABILITY Normal OCCURRENCE Found in a Vietnamese family OTHER INFORMATION Quantity in heterozygotes 9% of total Hb REFERENCES 1. Como, P.F., Barber, S., Sage, R.E., and Kronenberg, H.: Abstract, 29th Meeting of the Royal College of Pathologists of Australia, Melbourne, 1983. 2. Como, P.F., Barber, S., Sage, R.E., Trent, R.J., and Kronenberg, H.: Hemoglobin, 10:135, 1986. Hb Swan River alpha6(A4)Asp->Gly CONTACT External; partly buried HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X appeared as a band with a mobility between Hb F and Hb S on cellulose acetate electrophoresis at pH 8.6; no separation by citrate agar electrophoresis at pH 6.0 CHROMATOGRAPHY Hb A and Hb X are partially separated by DEAE-Sephadex or by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GGC; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly decreased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a Yugoslav woman, in a 24-year-old Caucasian female and her two children in the USA, and in a Japanese male OTHER INFORMATION Quantity in heterozygotes ~10% REFERENCES 1. Como, P.F., Wilkinson, T., Kronenberg, H., Raven, J.L., Prior, J., and Trent, R.J.: Hemoglobin, 13:393, 1989. 2. Moo-Penn, W.F., Jue, D.J., Johnson, M.H., and Therrell, B.L.: Hemoglobin, 11: 61, 1987. 3. Harano, T., Harano, K., Imai, K., and Terunuma, S.: Hemoglobin, 20:75, 1996. Hb Tatras alpha7(A5)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Electrophoresis at alkaline pH showed a fast-moving Hb like Hb A1c CHROMATOGRAPHY A fast-moving Hb component was separated from Hb A by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; the peptides were separated by reversed phase HPLC; peptides alphaT-1 and alphaT-2 combined to form an alphaT-1,2 peptide; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a 72-year-old woman born in Czechoslovakia OTHER INFORMATION Quantity in the heterozygote 22% REFERENCES 1. Wajcman, H., Bost, M., Blouquit, Y., Prehu, C., Riou, J., and Galacteros, F.: Hemoglobin, 18:427, 1994. Hb Kurosaki alpha7(A5)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS IEF demonstrated the presence of Hb X as a fast-moving band that focused anodally to Hb A (almost at the position of Hb H) CHROMATOGRAPHY Fast-eluting Hb by cation exchange HPLC; Hb X and Hb A were also separated on a DEAE-5PW HPLC column STRUCTURE STUDIES The alpha chain was isolated by CM-cellulose 8 M-urea-phosphate chromatography; tryptic peptides were separated by reversed phase HPLC; an alphaT-1,2 peptide was identified (alphaT-1 and alphaT-2 were absent) by amino acid analysis; sequence analysis DNA ANALYSES Not reported; presumed mutation AAG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a 70-year-old diabetic Japanese female OTHER INFORMATION Quantity in the heterozygote 17.7% REFERENCES 1. Harano, T., Harano, K., Imai, K., Murakami, T., and Matsubara, H.: Hemoglobin, 19:197, 1995. Hb Anantharaj alpha11(A9)Lys->Glu MISDIAGNOSED CORRECT SUBSTITUTION alpha11(A9)Lys->Gln = Hb J-Wenchang-Wuming REFERENCES 1. Pootrakul, S., Kematorn, B., Na-Nakorn, S., and Suanpan, S.: Biochim. Biophys. Acta, 405:161, 1975. 2. Svasti, J., Surarit, R., Srisomsap, C., Pravatmuang, P., Wasi, P., Fucharoen, S., Blouquit, Y., Galacteros, F., and Rosa, J.: Hemoglobin, 17:453, 1993. Hb J-Wenchang-Wuming alpha11(A9)Lys->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH (8.6) CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->CAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in five persons in a Chinese family OTHER INFORMATION Quantity in heterozygotes 20% REFERENCES 1. Chen, S-S., Liang, L-L., Jia, P-C., Yang, K-G., Chen, L-C., and Chen, L-F.: Zhongguo Kexue (series B), 26(3):243, 1983. 2. Zeng, Y-T., Huang, S-Z., Liang, X., Long, G-F., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 5:679, 1981. Hb Albany-Suma alpha11(A9)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on starch gel (pH 9.0) and cellulose acetate (pH 8.9); it moves with Hb A on citrate agar (pH 6.0) CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a 15-year-old Black female OTHER INFORMATION Quantity in the heterozygote 23.8% REFERENCES 1. Webber, B.B., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 7:257, 1983. 2. Shimasaki, S., Iuchi, I., Hidaka, K., and Mizuta, W.: Jpn. J. Hum. Genet., 28:127, 1983. Hb J-Paris-I alpha12(A10)Ala->Asp ALSO KNOWN AS J-Aljezur CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on starch gel and cellulose acetate (pH 8.6); it moves with Hb A on agar gel CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; Edman-degradation DNA ANALYSES Mutations in both the alpha2 and alpha1 genes: GCC->GAC at codon 12 (Ref. 6) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in Spanish, Portuguese, Iranian, Yugoslavian, and Punjabi families OTHER INFORMATION Quantity in heterozygotes 26.6% REFERENCES 1. Rosa, J., Maleknia, N., Vergoz, D., and Dunet, R.: Nouv. Rev. Fr. d'Hematol., 6: 423, 1965. 2. Trincao, C., Martins de Melo, J., Lorkin, P.A., and Lehmann, H.: Acta Haematol., 39:291, 1968. 3. Rahbar, S., Sooudi, H., and Daneshmand, P.: Acta Haematol., 47:43, 1972. 4. Niazi, G.A., Efremov, G.D., Nikolov, N., Hunter, E., and Huisman, T.H.J.: Biochim. Biophys. Acta, 412:181, 1975. 5. Dash, S. and Huisman, T.H.J.: Acta Haematol., 79:117, 1988. 6. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Evanston alpha14(A12)Trp->Arg CONTACT Internal HEMATOLOGY Mild anemia; microcytosis; associated with alpha-thal-2 ELECTROPHORESIS Migrates to the position of Hb S at alkaline pH; no separation from Hb A by citrate agar at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGG->AGG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; Bohr and cooperativity effects normal STABILITY Normal OCCURRENCE Found in two Black families OTHER INFORMATION Quantity in heterozygotes not clearly established REFERENCES 1. Honig, G.R., Shamsuddin, M., Vida, L.N., Mompoint, M., Bowie, L., Jones, E., and Weil, S.: Blood, 60:53a (Suppl. 1), 1982. 2. Moo-Penn, W.F., Baine, R.M., Jue, D.L., Johnson, M.H., McGuffey, J.E., and Benson, J.M.: Biochim. Biophys. Acta, 747:65, 1983. Hb I-Interlaken alpha15(A13)Gly->Asp ALSO KNOWN AS J-Oxford; N-Cosenza CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X can be separated from Hb A by starch block, cellulose acetate, and starch gel at pH 8.6, but not by agar gel at pH 6.2 CHROMATOGRAPHY Hb X can be isolated from Hb A by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and/or cation exchange chromatography; amino acid analysis; carboxypeptidase A and B digestion; Edman degradation DNA ANALYSES Mutation in the alpha1 gene: GGT->GAT at codon 15 (Ref. 4) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in Italian families, American Italians, and an English family OTHER INFORMATION Quantity in heterozygotes 16-23%; found in combination with beta-thal REFERENCES 1. Marti, H.R., Pik, C., and Mosimann, P.: Acta Haematol., 32:9, 1964. 2. Liddell, J., Brown, D., Beale, D., Lehmann, H., and Huntsman, R.G.: Nature, 204:269, 1964. 3. Schiliro, G., Musumeci, S., Pizzarelli, G., Russo, A., Marinucci, M., Bruni, E., and Russo, G.: Blood, 48:639, 1976. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Ottawa alpha15(A13)Gly->Arg ALSO KNOWN AS Siam CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves close to Hb S on paper (pH 8.9) and with Hb A on citrate agar (pH 6.1); it is slower than Hb F on starch gel (pH 8.6) CHROMATOGRAPHY Hb X can be isolated from Hb A by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase B digestion DNA ANALYSES Not reported; presumed mutation GGT->CGT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Polish-Canadian family and in a Chinese male from Thailand OTHER INFORMATION Quantity in heterozygotes 15-25% REFERENCES 1. Vella, F., Casey, R., Lehmann, H., Labossierre, A., and Jones, T.G.: Biochim. Biophys. Acta, 336:25, 1974. 2. Pootrakul, S., Srichiyanont, S., Wasi, P., and Suanpan, S.: Humangenetik, 23:199, 1974. Hb I alpha16(A14)Lys->Glu ALSO KNOWN AS I-Philadelphia; I-Texas; I-Burlington; I-Skamania CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves ahead of Hb A at alkaline pH and with Hb A at acidic pH (citrate agar) CHROMATOGRAPHY Hb X can be separated from Hb A by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Mutation in the alpha2 gene: AAG->GAG at codon 16 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in Blacks, Indians, and Caucasian families OTHER INFORMATION Quantity in heterozygotes 24-28% REFERENCES 1. Beale, D. and Lehmann, H.: Nature, 207:259, 1965. 2. Folayan Esan, G.J., Morgan, F.J., O'Donnell, J.V., Ford, S., and Bank, A.: J. Clin. Invest., 49:2218, 1970. 3. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Beijing alpha16(A14)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves ahead of Hb A at alkaline pH; it moves between Hb A and Hb H, probably at position of Hb J on cellulose acetate (pH 8.6) CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing of selected peptides DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Chinese family OTHER INFORMATION Quantity in heterozygotes 19.3% REFERENCES 1. Liang, C.C., Chen, S., Yang, K., Jia, P., Ma, Y., Li, T., Ni, X., Wang, X., Deng, Q., and Yao, S.: Hemoglobin, 6:629, 1982. Hb Harbin alpha16(A14)Lys->Met CONTACT External HEMATOLOGY Proband was anemic ELECTROPHORESIS Hb X was identified as a fast-moving band with a mobility like Hb J; the variant moves ahead of Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis of a few tryptic peptides DNA ANALYSES Not reported; presumed mutation AAG->ATG; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly increased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a 30-year-old Chinese woman OTHER INFORMATION Quantity in the heterozygote 18% REFERENCES 1. Zeng, Y-T., Huang, S-Z., Qiu, X-K., Cheng, G-C., Ren, Z-R., Jin, Q-C., Chen, C-Y., Jiao, C-T., Tang, Z-G., Liu, R-H., Bao, X-H., Zeng, L-Z., Duan, Y-Q., and Zhang, G-Y.: Hemoglobin, 8:569, 1984. Hb Handsworth alpha18(A16)Gly->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly slower than Hb A on paper at alkaline pH (8.9); it moves to the position of Hb G on cellulose acetate (pH 9.0) CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing of a few selected peptides DNA ANALYSES Not reported; presumed mutation GGC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in an Indian family, a Chinese family, and a Saudi newborn OTHER INFORMATION Quantity in heterozygotes: 9-11% (Indian), 32% (Chinese), and 20.8% (Saudi newborn) REFERENCES 1. Griffiths, K.D., Lang, A., Lehmann, H., Mann, J.R., Plowman, D., and Raine, D.N.: FEBS Lett., 75:93, 1977. 2. Liang, C-C., Tao, H-N., and Chang, K-F.: Hemoglobin, 5:191, 1981. 3. Al-Awamy, B.H., Niazi, G.A., Naeem, M.A., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 9:183, 1985. Hb Al-Ain Abu Dhabi alpha18(A16)Gly->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a family living in the United Arab Emirates OTHER INFORMATION Quantity in heterozygotes 25-31.6% REFERENCES 1. Abbes, S., M'Rad, A., Fitzgerald, P.A., Dormer, P., Blouquit, Y., Kister, J., Galacteros, F., and Wajcman, H.: Hemoglobin, 16:355, 1992. Hb J-Kurosh alpha19(AB1)Ala->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on cellulose acetate and starch gel CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis of selected peptides DNA ANALYSES Not reported; presumed mutation GCG->? (undefined); GCC-> GAC?; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a healthy Iranian male OTHER INFORMATION Quantity in the heterozygote 25% NOTE Codon 19 is presumed to be GCG but may be GCC in some populations; a one base change of GCC can result in GAC and explain the Ala->Asp replacement REFERENCES 1. Rahbar, S., Ala, F., Akhavan, E., Nowzari, G., Shoa'i, I., and Zamanianpoor, M.H.: Biochim. Biophys. Acta, 427:119, 1976. Hb J-Tashikuergan alpha19(AB1)Ala->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A as a fast moving band on cellulose acetate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in three families of the Tajike ethnic group; emigres from Afghanistan OTHER INFORMATION Quantity in heterozygotes 18.9-22.7% REFERENCES 1. Li, H., Liu, D., Liu, Z., Li, P., Li, L., Chen, J., and Hou, S.: Hemoglobin, 8:391, 1984. Hb Necker Enfants-Malades alpha20(B1)His->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves with Hb A on cellulose acetate and citrate agar; separation is best by IEF (pI 6.84; Hb A pI 6.95) CHROMATOGRAPHY The variant was isolated on a Bio-Rex 70 column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Not reported OCCURRENCE Found in a family from the French West Indies (Guadeloupe) OTHER INFORMATION Quantity in the heterozygote 30% REFERENCES 1. Wajcman, H., Elion, J., Boissel, J.P., Labie, D., Jos, J., and Girot, R.: Hemoglobin, 4:177, 1980. Hb Le Lamentin alpha20(B1)His->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves with Hb A on cellulose acetate (pH 8.6) and citrate agar (pH 6.0); it is more anodal than Hb A1c on IEF CHROMATOGRAPHY Hb X was isolated on a Bio-Rex 70 column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Mutation in the alpha2 gene: CAC->CAA at codon 20 (Ref. 4) FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in families from Martinique, Japan, and Spain OTHER INFORMATION Quantity in heterozygotes 20% REFERENCES 1. Sellaye, M., Blouquit, Y., Galacteros, F., Arous, N., Monplaisir, N., Rhoda, M.D., Braconnier, F., and Rosa, J.: FEBS Lett., 145:128, 1982. 2. Harano, T., Harano, K., Shibata, S., Ueda, S., Imai, K., Tsuneshige, A., Uchida, E., and Horiuchi, K.: Hemoglobin, 7:181, 1983. 3. Malcorra-Azpiazu, J.J., Balda-Aguirre, M.I., Diaz-Chico, J.C., Kutlar, F., Kutlar, A., Hu, H., and Huisman, T.H.J.: Hemoglobin, 12:201, 1988. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Hobart alpha20(B1)His->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A as a slowly-moving band at alkaline pH; its mobility is similar to that of Hb Lepore or Hb S CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a family of British nationality OTHER INFORMATION Quantity in the heterozygote 16-18% REFERENCES 1. Fleming, P.J., Sumner, D.R., Wyatt, K., Hughes, W.G., Melrose, W.D., Jupe, D.M.D., and Baikie, M.J., Hemoglobin, 11:211, 1987. Hb J-Nyanza alpha21(B2)Ala->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on paper at alkaline pH (8.9) CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCT->GAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a family from Western Kenya OTHER INFORMATION Quantity in heterozygotes as high as 35% because of a co-existing alpha-thal REFERENCES 1. Kendall, A.G., Barr, R.D., Lang, A., and Lehmann, H.: Biochim. Biophys. Acta, 310:357, 1973. Hb Fontainebleau alpha21(B2)Ala->Pro CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS IEF reveals an abnormal band that migrates like Hb A1c CHROMATOGRAPHY No separation of Hb X and Hb A by CM-cellulose chromatography and reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCT->CCT; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal; the Ala->Pro replacement occurs at the second position of the B helix OCCURRENCE Found in an Italian family OTHER INFORMATION No definitive information about the quantity in the heterozygote; may be as high as 25-28% REFERENCES 1. Wajcman, H., Blouquit, Y., Gombaud-Saintonge, G., Riou, J., and Galacteros, F.: Hemoglobin, 13:421, 1989. Hb J-Medellin alpha22(B3)Gly->Asp CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb X moves faster than Hb J at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in two families from Colombia OTHER INFORMATION Quantity in heterozygotes 20% REFERENCES 1. Gottlieb, A.J., Restrepo, A., and Itano, H.A., Fed. Proc., 23:172, 1964. Hb Memphis alpha23(B4)Glu->Gln CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb X moves to the position of Hb S at both alkaline and acidic pH; it moves slightly cathodal to Hb S on agar gel at pH 6.2 and 7.2 CHROMATOGRAPHY Not studied in detail STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->CAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a few Black families OTHER INFORMATION Found in combination with Hb S and Hb C; combination with the Hb S condition might be milder than the common sickle cell anemia REFERENCES 1. Kraus, A.P., Miyaji, T., Iuchi, I., and Kraus, L.M.: J. Lab. Clin. Med., 66:886, 1965. 2. Kraus, L.M., Miyaji, T., Iuchi, I., and Kraus, A.P.: Biochemistry, 5:3701, 1966. 3. Cooper, M.R., Kraus, A.P., Felts, J.H., Ramseur, W.L., Myers, R., and Kraus, L.P.: Am. J. Med., 55:535, 1973. Hb Chad alpha23(B4)Glu->Lys ALSO KNOWN AS E-Keelung CONTACT External HEMATOLOGY Normal in heterozygotes without alpha-thal ELECTROPHORESIS Hb X moves to the position of Hb E or Hb A2 on starch gel at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X separates from Hb A in cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES A GAG->AAG mutation at codon 23 of the -alpha(3.7 kb) alpha-thal-2 gene has been reported in a family from Surinam (Ref. 3) FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Reported in a few Black, Chinese, and Japanese families OTHER INFORMATION Quantity in heterozygotes 14.5-24%; those with the mutation on the -alpha(3.7 kb) alpha-thal-2 gene had ~31.5% Hb X REFERENCES 1. Boyer, S.H., Crosby, E.F., Fuller, G.F., Ulenurm, L., and Buck, A.A.: Am. J. Hum. Genet., 20:570, 1968. 2. Blackwell, R.Q., Weng, M-I., and Huang, J-T.: Trop. Geogr. Med., 25:393, 1973. 3. Codrington, J.F., Codrington, F.A., Wisse, J.H., Wilson, J.B., Webber, B.B., Wong, S.C., and Huisman, T.H.J.: Hemoglobin, 13:543, 1989. Hb G-Audhali alpha23(B4)Glu->Val CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb G at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GTG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in two Black families living in Southern Arabia OTHER INFORMATION Quantity in heterozygotes ~25% REFERENCES 1. Marengo-Rowe, A.J., Beale, D., and Lehmann, H.: Nature, 219:1164, 1968. Hb Reims alpha23(B4)Glu->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH; good separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on an HPLC column; amino acid analysis; sequencing of the alphaT-4 peptide DNA ANALYSES Not reported; presumed mutation GAG->GGG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Slightly unstable OCCURRENCE Found in a 60-year-old French woman OTHER INFORMATION Quantity in the heterozygote ~31% REFERENCES 1. Bardakdjian-Michau, J., Rosa, J., Galacteros, F., Lancelot, M., and Marquart, F.X.: Hemoglobin, 13:733, 1989. Hb Lisbon alpha23(B4)Glu->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS The best separation of Hb X and Hb A is by IEF; the electrophoretic pattern showed a slight decrease in pI CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on an HPLC column; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a 31-year-old Portuguese male OTHER INFORMATION Quantity in the heterozygote not reported REFERENCES 1. Wajcman, H., Bost, M., Blouquit, Y., Prehu, C., Riou, J., and Galacteros, F.: Hemoglobin, 18:427, 1994. Hb Luxembourg alpha24(B5)Tyr->His CONTACT Internal HEMATOLOGY Mild hemolysis; reticulocytosis; no anemia in the heterozygote ELECTROPHORESIS Hb X migrates with a pI similar to Hb A1c on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on an HPLC column; amino acid analysis DNA ANALYSES Not reported; presumed mutation TAT->CAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in two Dutch families OTHER INFORMATION Quantity in the heterozygote estimated at 20-22% REFERENCES 1. Groff, P., Galacteros, F., Kalmes, G., Blouquit, Y., and Wajcman, H.: Hemoglobin, 13:429, 1989. 2. Moo-Penn, W.F., Hine, T.K., Johnson, M.H., Jue, D.L., Piersma, H., Therrell, B., Jr., and Chu, A.: Hemoglobin, 15:97, 1991. Hb Ramona alpha24(B5)Tyr->Cys CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X was detected by IEF; it moves slightly faster than Hb A CHROMATOGRAPHY No separation by cation or anion exchange chromatography STRUCTURE STUDIES No separation from Hb A by cation exchange HPLC; no protein analysis reported DNA ANALYSES Mutation in the alpha1 gene: TAT->TGT at codon 24 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a female of Spanish descent OTHER INFORMATION Quantity in the heterozygote could not be determined REFERENCES 1. Pobedimskaya, D.D., Molchanova, T.P., and Huisman, T.H.J.: Hemoglobin, 18: 365, 1994. Hb Shenyang alpha26(B7)Ala->Glu CONTACT Internal HEMATOLOGY Anemia in the heterozygote; some target cells ELECTROPHORESIS Hb X moves like Hb J on cellulose acetate and starch gel at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing analysis DNA ANALYSES Not reported; presumed mutation GCG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in a 23-year-old Chinese male OTHER INFORMATION Quantity in the heterozygote 21.5% REFERENCES 1. Zeng, Y-T., Huang, S-Z., Zhou, X-D., Qiu, X-K., Dong, Q-Y., Li, M-Y., and Bai, J-H.: Hemoglobin, 6:625, 1982. Hb Fort Worth alpha27(B8)Glu->Gly CONTACT External; surface crevice HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb S at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GGG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Inconclusive OCCURRENCE Found in a few Black families OTHER INFORMATION Quantity in heterozygotes 4-5% REFERENCES 1. Schneider, R.G., Brimhall, B., Jones, R.T., Bryant, R., Mitchell, C.B., and Goldberg, A.I.: Biochim. Biophys. Acta, 243:164, 1971. 2. Carstairs, K.C., Raulfs, A., Kutlar, A., Chen, S.S., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 9:201, 1985. Hb Spanish Town alpha27(B8)Glu->Val CONTACT External; surface crevice HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb F at alkaline pH; like Hb A at acidic pH CHROMATOGRAPHY The variant was isolated by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GTG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal to mildly unstable OCCURRENCE Found in a Black Jamaican family OTHER INFORMATION Quantity in heterozygotes 11-12% REFERENCES 1. Ahern, E., Ahern, V., Holder, W., Palomino, E., Serjeant, G.R., Serjeant, B.E., Forbes, M., Brimhall, B., and Jones, R.T.: Biochim. Biophys. Acta, 427:530, 1976. Hb Shuangfeng alpha27(B8)Glu->Lys CONTACT External; surface crevice HEMATOLOGY Hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb C on cellulose acetate (pH 8.6); moves with Hb A on citrate agar (pH 6.0) CHROMATOGRAPHY Hb X was isolated by DE-52 cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->AAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in six members of a Chinese family OTHER INFORMATION Quantity in heterozygotes about 13% REFERENCES 1. Liang, C., Tao, H., Lo, H., Huang, S., Li, R., and Wang, B.: Hemoglobin, 5:691, 1981. Hb Hekinan alpha27(B8)Glu->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS IEF reveals a fast-moving abnormal band CHROMATOGRAPHY Hb X separates from Hb A by cation exchange chromatography; the separation is incomplete on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on filter paper or by reversed phase HPLC; amino acid analysis DNA ANALYSES Mutation in the alpha2 gene: GAG->GAC at codon 27 (Ref. 4) FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a Japanese male; in a woman from French Guyana (of Chinese-Black descent), and in three Chinese families from Macao OTHER INFORMATION Quantity in heterozygotes 13-14% REFERENCES 1. Harano, T., Harano, K., Imai, N., Ueda, S., and Seki, M.: Hemoglobin, 12:61, 1988. 2. Merault, G., Keclard, L., Desfontaines, L., Saint-Martin, C., Blouquit, Y., Rosa, J., and Galacteros, F.: Hemoglobin, 13:397, 1989. 3. Zhao, W., Wilson, J.B., Webber, B.B., Kutlar, A., Tamagnini, G.P., Kuam, B., and Huisman, T.H.J.: Hemoglobin, 14:627, 1990. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Agrinio alpha29(B10)Leu->Pro CONTACT Internal HEMATOLOGY Microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X is not detectable CHROMATOGRAPHY Hb X is not detectable STRUCTURE STUDIES Not possible DNA ANALYSES Hb X was identified by sequencing of amplified DNA; a CTG->CCG mutation at codon 29 of the alpha2 gene FUNCTIONAL STUDIES Not possible STABILITY Unstable because of the introduction of a proline residue in the middle of the B helix OCCURRENCE Found in three Greek Cypriots OTHER INFORMATION The patients had atypical Hb H disease, severe anemia, hypochromia, and microcytosis REFERENCES 1. Hall, G.W., Thein, S.L., Newland, A.C., Chisholm, M., Traeger-Synodinos, J., Kanavakis, E., Kattamis, C., and Higgs, D.R.: Br. J. Haematol., 85:546, 1993. Hb O-Padova alpha30(B11)Glu->Lys CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb C (closer to Hb C) on starch gel, cellulose acetate, and citrate agar at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex or DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or on a reversed phase column; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->AAG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in members of an Italian and a Turkish family OTHER INFORMATION Quantity in heterozygotes 12.6-18% REFERENCES 1. Vettore, L., DeSandre, G., Dilorio, E.E., Winterhalter, K.H., Lang, A., and Lehmann, H.: Blood, 44:869, 1974. 2. Kilinc, Y., Kumi, M., Gurgey, A., Altay, C., Webber, B.B., Wilson, J.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 9:621, 1985. Hb G-Honolulu alpha30(B11)Glu->Gln ALSO KNOWN AS G-Singapore; G-Chinese; G-Hong Kong CONTACT alpha1beta1 contact HEMATOLOGY Normal in heterozygotes ELECTROPHORESIS Hb X moves about as Hb S at alkaline pH; no separation at acidic pH CHROMATOGRAPHY Hb X separates from Hb A on cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->CAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in several Chinese families OTHER INFORMATION Quantity in heterozygotes 12-15% REFERENCES 1. Vella, F., Ager, J.A.M., and Lehmann, H.: Nature, 182:460, 1958. 2. Schneider, R.G. and Jim, R.T.S.: Nature, 190:454, 1961. 3. Swenson, R.T., Hill, R.L., Lehmann, H., and Jim, R.T.S.: J. Biol. Chem., 237: 1517, 1962. 4. Zeng, Y.T., Huang, S.Z., Zhou, X.D., Feng, J.P., Chen, M.J., Sheng, M., Qiu, X.K., Tao, Y.J., Chen, B.F., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Shanghai Med. J., 5:125, 1982. Hb Prato alpha31(B12)Arg->Ser CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH but does not separate at acidic pH CHROMATOGRAPHY Hb X separates from Hb A by DE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on paper or reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGG->AGC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Mildly unstable OCCURRENCE Found in two Italian families OTHER INFORMATION Quantity in heterozygotes 20-30% REFERENCES 1. Marinucci, M., Mavilio, F., Massa, A., Gabbianelli, M., Fontanarosa, P.P., Camagna, A., Ignesti, C., and Tentori, L.: Biochim. Biophys. Acta, 578:534, 1979. 2. De Marco, E.V., Crescibene, L., Pascua, A., Brancati, C., Bria, M., and Qualtieri, A.: Hemoglobin, 16:275, 1992. Hb Queens alpha34(B15)Leu->Arg ALSO KNOWN AS Ogi CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A as a slowly-moving variant at alkaline pH; it also separates from Hb A at acidic pH; moves between Hb S and Hb F on cellulose acetate and starch gel; moves between Hb A and Hb S on agar gel CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly increased oxygen affinity; normal Bohr effect and cooperativity STABILITY Mildly unstable OCCURRENCE Found in Korean, Chinese, Japanese, Vietnamese, and Thai families OTHER INFORMATION Quantity in heterozygotes 10-16% REFERENCES 1. Tatsis, B.: Blood, 54:61a (Suppl. 1), 1979. 2. Zeng, Y-T., Huang, S-Z., Yen, Y-K., Li, W-C., Lam, H., Webber, B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 6:209, 1982. 3. Sugihara, J., Imamura, T., Yamada, H., Imoto, T., Matsuo, T., Sumida, I., and Yanase, T.: Biochim. Biophys. Acta, 701:45, 1982. 4. Yongsuwan, S., Svasti, J., and Fucharoen, S.: Hemoglobin, 11:567, 1987. Hb Bourmedes alpha37(C2)Pro->Arg CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A at alkaline pH; its mobility is between Hb S and Hb A2; excellent separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not studied STABILITY Not studied OCCURRENCE Found in an Algerian family; the proband was also homozygous for Hb S OTHER INFORMATION Quantity in the heterozygote 16-20% REFERENCES 1. Dahmane-Arbane, M., Blouquit, Y., Arous, N., Bardakdjian, J., Benamani, M., Riou, J., Benabadji, M., Rosa, J., and Galacteros, F.: Nouv. Rev. Fr. d'Hematol., 29:317, 1987. Hb Kariya alpha40(C5)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A as a fast-moving variant at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on paper or by reversed phase HPLC; amino acid analysis; sequencing of the alphaT-5,6 peptide DNA ANALYSES Not reported; presumed mutation AAG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased heme-heme interaction, 2,3-DPG, and Bohr effect STABILITY Mildly unstable OCCURRENCE Found in a Japanese family; also an American Caucasian family OTHER INFORMATION Quantity in heterozygotes 14-19% REFERENCES 1. Harano, T., Harano, K., Shibata, S., Ueda, S., Imai, K., Tsuneshige, A., Yamada, H., Seki, M., and Fukui, H.: FEBS Lett., 153:332, 1983. 2. Nakatsuji, T., Headlee, M.G., and Huisman, T.H.J.: Hemoglobin, 8:401, 1984. Hb Kanagawa alpha40(C5)Lys->Met CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A at alkaline pH as a fast-moving variant; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A1c elute together by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Mutation in the alpha2 gene: AAG->ATG at codon 40 FUNCTIONAL STUDIES Increased oxygen affinity, decreased heme-heme interaction and 2,3-DPG effect STABILITY Normal OCCURRENCE Found in a 70-year-old Japanese male OTHER INFORMATION Quantity in the heterozygote about 15% REFERENCES 1. Miyashita, H., Hashimoto, K., Mohri, H., Ohokubo, T., Harano, T., Harano, K., and Imai, K.: Hemoglobin, 16:1, 1992. Hb Miyano alpha41(C6)Thr->Ser CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS Separation of Hb X and Hb A only by IEF CHROMATOGRAPHY Hb X and Hb A could not be separated by either anion or cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on a cation exchange HPLC column; amino acid analysis; acid hydrolysis of the alphaT-6 peptide DNA ANALYSES Not reported; presumed mutation ACC->TCC or AGC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a Japanese male blood donor, born in 1931 OTHER INFORMATION None REFERENCES 1. Ohba, Y., Imai, K., Uenaka, R., Ami, M., Fujisawa, K., Itoh, K., Hirakawa, K., and Miyaji, T.: Hemoglobin, 13:637, 1989. Hb Torino alpha43(CE1)Phe->Val CONTACT Heme contact HEMATOLOGY Heinz body hemolytic anemia ELECTROPHORESIS Separation of Hb X and Hb A is most difficult; Hb X moves with Hb A on paper (pH 8.9) and on starch gel at alkaline pH; data obtained by IEF are not available CHROMATOGRAPHY Data obtained by HPLC procedures are not available STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting, amino acid analysis; sequencing of a selected peptide DNA ANALYSES Not reported; presumed mutation TTC->GTC; alpha2 or alpha1 FUNCTIONAL STUDIES No data for the isolated Hb X STABILITY Unstable OCCURRENCE Found in a few Italian families OTHER INFORMATION Quantity in heterozygotes difficult to determine; it is estimated at ~10%; anemia is drug induced REFERENCES 1. Beretta, A., Prato, V., Gallo, E., and Lehmann, H.: Nature, 217:1016, 1968. 2. Prato, V., Gallo, E., Ricco, G., Mazza, U., Bianco, G., and Lehmann, H.: Br. J. Haematol., 19:105, 1970. 3. Sansone, G., Sciarratta, G.V., Lang, A., Lorkin, P.A., and Lehmann, H.: Acta Haematol., 56:225, 1976. Hb Hirosaki alpha43(CE1)Phe->Leu CONTACT Heme contact HEMATOLOGY Congenital non-spherocytic hemolytic anemia ELECTROPHORESIS Hb X and Hb A difficult to separate; Hb X moves with Hb A on agar gel at pH 8.6 and 7.0; data for IEF are not available CHROMATOGRAPHY Data for HPLC procedures are not available STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing of a selected peptide DNA ANALYSES Not reported; presumed mutation TTC->CTC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in several members of a Japanese (?) family OTHER INFORMATION Quantity in heterozygotes difficult to determine; it is estimated at ~10% REFERENCES 1. Ohba, Y., Miyaji, T., Matsuoka, M., Yokoyama, M., Numakura, H., Nagata, K., Takebe, Y., Izumi, Y., and Shibata, S.: Biochim. Biophys. Acta, 405:155, 1975. 2. Ohba, Y., Miyaji, T., Matsuoka, M., and Yokoyama, M.: Hemoglobin, 2:281, 1978. Hb Milledgeville alpha44(CE2)Pro->Leu CONTACT External HEMATOLOGY Mild erythrocytosis ELECTROPHORESIS Hb X and Hb A did not separate by electrophoretic methods, including IEF CHROMATOGRAPHY Hb X did not separate by CM-cellulose or IRC-50; no abnormal globin chain could be isolated STRUCTURE STUDIES Fingerprinting of peptides obtained by proteolysis of the entire alpha chain; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCG->CTG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity, normal Bohr effect, reduced cooperativity (analyses of freshly collected blood) STABILITY Normal OCCURRENCE Found in three members of a Black family OTHER INFORMATION Quantity in the heterozygote could not be determined REFERENCES 1. Honig, G.R., Vida, L.N., Shamsuddin, M., Mason, R.G., Schlumpf, H.W., and Luke, R.A.: Biochim. Biophys. Acta, 626:424, 1980. Hb Kawachi alpha44(CE2)Pro->Arg CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb A and Hb X separate at alkaline pH; Hb X is present between Hb A2 and Hb A on IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCG->CGG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity, reduced Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in three members of a Japanese family OTHER INFORMATION Quantity in heterozygotes 26-27% REFERENCES 1. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., Ohba, Y., Shinohara, T., Horio, S., Nishioka, K., and Shirotani, H.: Hemoglobin, 6:43, 1982. Hb Fort de France alpha45(CE3)His->Arg CONTACT External; heme contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (moves as Hb S on cellulose acetate); good separation by IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; peptides were separated by fingerprinting or cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; normal Bohr effect and cooperativity STABILITY Unstable OCCURRENCE Found in two unrelated families living in Martinique OTHER INFORMATION Quantity in the heterozygote 20%; increased autoxidation REFERENCES 1. Braconnier, F., Gacon, G., Thillet, J., Wajcman, H., Soria, J., Maigret, P., Labie, D., and Rosa, J.: Biochim. Biophys. Acta, 493:228, 1977. Hb Bari alpha45(CE3)His->Gln CONTACT External; heme contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves with Hb A on cellulose acetate (pH 8.4) and on citrate agar CHROMATOGRAPHY Hb X did not separate by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CAG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Normal OCCURRENCE Found in an Italian male OTHER INFORMATION Quantity in the heterozygote was estimated at about 20% REFERENCES 1. Marinucci, M., Mavilio, F., Tentori, L., D'Erasmo, F., Colapietro, A., De Stasio, G., and Di Fonzo, S.: Biochim. Biophys. Acta, 622:315, 1980. Hb Poitiers alpha45(CE3)His->Asp CONTACT External; heme contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A as a fast-moving band at alkaline pH; no separation at acidic pH; IEF is an excellent procedure to identify Hb X CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of alphaA chain; separation of tryptic peptides by reversed phase HPLC; amino acid analysis; sequencing of the alphaT-6 peptide DNA ANALYSES Not reported; presumed mutation CAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity and autoxidation STABILITY Normal OCCURRENCE Found in three members of a French family OTHER INFORMATION Quantity in the heterozygote was ~27% REFERENCES 1. Bardakdjian, J., Kister, J., Wajcman, H., Boulard, P., Bohn, B., Blouquit, Y., and Galacteros, F.: Hemoglobin, 18:1, 1994. Hb Beilinson alpha47(CE5)Asp->Gly ALSO KNOWN AS Umi; Michigan-I; Michigan-II; Yukuhashi-II; L-Gaslini; Tagawa-II; Kokura; Mugino CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb S and Hb F on starch gel; moves slightly faster than Hb S on paper; moves slightly ahead of Hb S on cellulose acetate CHROMATOGRAPHY Hb X can be isolated by DEAE-Sephadex and IRC-50 chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GGC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in Ashkenazi Jews and Japanese families OTHER INFORMATION Quantity in heterozygotes 11-17% REFERENCES 1. DeVries, A., Joshua, H., Lehmann, H., Hill, R.L., and Fellows, R.E.: Br. J. Haematol., 9:484, 1963. 2. Sumida, I.: Jpn. J. Hum. Genet., 19:343, 1975. 3. Ohba, Y., Hattori, Y., Matsuoka, M., Miyaji, T., and Fuyuno, K.: Hemoglobin, 6: 69, 1982. Hb Hasharon alpha47(CE5)Asp->His ALSO KNOWN AS Sinai; Sealy; L-Ferrara CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at both alkaline and acidic pH; moves as Hb S on paper, starch gel, and cellulose acetate; moves between Hb S and Hb C on citrate agar CHROMATOGRAPHY Hb X can be separated from Hb A by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic peptides were separated by fingerprinting or by cation exchange chromatography; amino acid analysis DNA ANALYSES Mutation in the alpha2 gene: GAC->CAC at codon 47 (Ref. 4) FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in Ashkenazi Jews and Italian families OTHER INFORMATION Quantity in heterozygotes 14-19% (Jews) REFERENCES 1. Halbrecht, I., Isaacs, W.A., Lehmann, H., and Ben-Porat, F.: Israel J. Med. Sci., 3:827, 1967. 2. Ostertag, W. and Smith, E.W.: Humangenetik, 6:377, 1968. 3. Schneider, R.G., Ueda, S., Alperin, J.B., Brimhall, B., and Jones, R.T.: Am. J. Hum. Genet., 20:151, 1968. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Arya alpha47(CE5)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH but not at acidic pH; moves with Hb S on cellulose acetate; moves as Hb S on starch gel CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in an Iranian family OTHER INFORMATION Quantity in heterozygotes 22% REFERENCES 1. Rahbar, S., Mahdavi, N., Nowzari, G., and Mostafavi, I.: Biochim. Biophys. Acta, 386:525, 1975. Hb Cordele alpha47(CE5)Asp->Ala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb S at alkaline pH (cellulose acetate) CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES The tryptic peptides were separated by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GCC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Mildly unstable OCCURRENCE Found in a Black family OTHER INFORMATION Quantity in heterozygotes 21-23% REFERENCES 1. Nakatsuji, T., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 8:37, 1984. Hb Kurdistan alpha47(CE5)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH CHROMATOGRAPHY Hb X was isolated by anion exchange chromatography STRUCTURE STUDIES Tryptic peptides of the alpha chain were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Mutation in the alpha2 gene: GAC->TAC at codon 47 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in three members of a Kurdish family OTHER INFORMATION Quantity in heterozygotes 17-18%; quantity of Hb X in one member who was also heterozygous for betao-thal was a low 4.2%, indicating a decreased affinity of alphaX for beta REFERENCES 1. Giordano, P.C., Harteveld, C.L., Streng, H., Oosterwijk, J.C., Heister, J.G.A.M., Amons, R., and Bernini, L.F.: Hemoglobin, 18:11, 1994. Hb Montgomery alpha48(CE6)Leu->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate by both alkaline and acidic pH; moves between Hb S and Hb F on cellulose acetate; moves as Hb G on starch gel; moves between Hb A and Hb S on citrate agar CHROMATOGRAPHY Hb X and Hb A separate by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography or reversed phase HPLC; amino acid analysis DNA ANALYSES Mutation in the alpha2 gene: CTG->CGG at codon 48 (Ref. 4) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in Black and Chinese families OTHER INFORMATION Quantity in heterozygotes 17-20% REFERENCES 1. Brimhall, B., Jones, R.T., Schneider, R.G., Hosty, T.S., Tomlin, G., and Atkins, R.: Biochim. Biophys. Acta, 379:28, 1975. 2. Huisman, T.H.J., Gravely, M.E., Wilson, J.B., Webber, B., Felice, A.E., and Miller, A.: Am. J. Hematol., 8:139, 1980. 3. Zeng, Y-T., Huang, S-Z., Dong, Z-Y., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 6:213, 1982. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Savaria alpha49(CE7)Ser->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline and acidic pH; Hb X moves as Hb S on starch gel CHROMATOGRAPHY Hb X separates from Hb A by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; the peptides were separated by fingerprinting; reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in Hungarian, Yugoslavian, and Kenyan families OTHER INFORMATION Quantity in heterozygotes 22-23% REFERENCES 1. Szelenyi, J.G., Horanyi, M., Foldi, J., Hudacsek, J., Istvan, L., and Hollan, S.R.: Hemoglobin, 4:27, 1980. 2. Juricic, D., Efremov, G.D., Wilson, J.B., and Huisman,T.H.J.: Hemoglobin, 9: 631, 1985. Hb J-Sardegna alpha50(CE8)His->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves as Hb J on cellogel CHROMATOGRAPHY Hb X and Hb A separate by chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in Italian families OTHER INFORMATION Quantity in heterozygotes ~20-22%; found in combination with beta-thal and with Hb G-Philadelphia REFERENCES 1. Tangheroni, W., Zorcolo, G., Gallo, E., and Lehmann, H.: Nature, 218:470, 1968. 2. Tangheroni, W., Zorcolo, G., Gallo, E., and Lehmann, H.: Helv. Paediatr. Acta, 24:174, 1969. 3. Gallo, E., Pugliatti, L., Ricco, G., Pich, P.G., Pinna, G., and Mazza, U.: Acta Haematol., 47:311, 1972. 4. Meloni, T., Pilo, G., Camardella, L., Cancedda, F., Lania, A., Pepe, G., and Luzzatto, L.: Blood, 55:1025, 1980. Hb Aichi alpha50(CE8)His->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can best be separated by IEF; Hb X moves slower than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a Japanese family OTHER INFORMATION Quantity in heterozygotes 21-22% REFERENCES 1. Harano, T., Harano, K., Shibata, S., Ueda, S., Mori, H., and Seki, M.: FEBS Lett., 169:297, 1984. Hb J-Abidjan alpha51(CE9)Gly->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS This fast-moving variant separates from Hb A at alkaline pH; moves to the position of Hb J on paper and cellulose acetate CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Yacouba male living at the Ivory Coast OTHER INFORMATION Quantity in heterozygotes about 23% REFERENCES 1. Cabannes, R., Renaud, R., Mauran, A., Pennors, H., Charlesworth, D., Price, B.G., and Lehmann, H.: Nouv. Rev. Fr. d'Hematol., 12:289, 1972. Hb Russ alpha51(CE9)Gly->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; moves as Hb S on starch gel CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic peptides of the alpha chain were separated by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in Caucasian families in the USA and in a Chinese family OTHER INFORMATION Quantity in heterozygotes 10-13% REFERENCES 1. Reynolds, C.A. and Huisman, T.H.J.: Biochim. Biophys. Acta, 130:541, 1966. 2. Chen, S-S., Yang, K-G., Jia, P-C., Liang, C-C., Huang, S-L., Liang, J-T., Chen, Q., and Li, H-H.: Acta Biochim. Biophys. Sin., 15(4):339, 1983. Hb J-Rovigo alpha53(E2)Ala->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH; Hb X does not separate from Hb A at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Probably normal OCCURRENCE Found in Italian and Brazilian families OTHER INFORMATION Quantity in heterozygotes 20-30%; found in combination with beta-thal REFERENCES 1. Alberti, R., Mariuzzi, G.M., Artibani, L., Bruni, E., and Tentori, L.: Biochim. Biophys. Acta, 342:1-1974. 2. Moo-Penn, W.F., Jue, D.L., and Baine, R.M.: Hemoglobin, 2:443, 1978. 3. Targino de Araujo, J., Plowman, D., Targino de Araujo, R.A., de Souza, L.F., and Lehmann, H.: Rev. Bras. Pesq. Med. Biol., 13:37, 1980. Hb Shimonoseki alpha54(E3)Gln->Arg ALSO KNOWN AS Hikoshima CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; the slow-moving variant has a mobility like Hb S; no separation at acidic pH CHROMATOGRAPHY Hb X was isolated on an Amberlite IRC-50 column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAA->CGA; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a Japanese family OTHER INFORMATION Quantity in heterozygotes 13-20% REFERENCES 1. Miyaji, T., Iuchi, I., Takeda, I., and Shibata, S.: Acta Haematol. Jpn., 26:531, 1963. 2. Hanada, M. and Rucknagel, D.L.: Blood, 24:624, 1964. 3. Imai, K., Morimoto, H., Kotani, M., Shibata, S., Miyaji, T., and Matsutomo, K.: Biochim. Biophys. Acta, 200:197, 1970. Hb Mexico alpha54(E3)Gln->Glu ALSO KNOWN AS J-Paris-II; Uppsala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on starch gel at alkaline pH CHROMATOGRAPHY Hb X was isolated on Bio-Rex 70 or DEAE-Sephadex columns STRUCTURE STUDIES The tryptic peptides were separated by cation exchange chromatography or by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAA->GAA; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in Mexican, Swedish, Algerian, Indian families, and a Black family in North Africa OTHER INFORMATION Quantity in heterozygotes ~20-25% (without alpha- or beta-thal); quantity in homozygotes 55%; found in combination with beta-thal, with Hb S, and with alpha-thal REFERENCES 1. Labie, D. and Rosa, J.: Nouv. Rev. Fr. d'Hematol., 6:426, 1965. 2. Jones, R.T., Brimhall, B., and Lisker, R.: Biochim. Biophys. Acta, 154:488, 1968. 3. Fessas, Ph., Kaltsoya, A., Loukopoulos, D., and Nilsson, L-O.: Hum. Hered., 19: 152, 1969. 4. Trabuchet, G., Pagnier, J., Benabadji, M., and Labie, D.: Hemoglobin, 1:13, 1976. 5. Tolstoshen, P., Williamson, R., Eskadale, J., Verdier, G., Godet, J., Nigon, V., Trabuchet, G., and Benabadji, M.: Eur. J. Biochem., 78:161, 1977. 6. Trabuchet, G., Benabadji, M., and Labie, D.: Hum. Genet., 42:189, 1978. Hb Thailand alpha56(E5)Lys->Thr CONTACT External; crevice HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves ahead of Hb A on starch gel at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ACG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Not reported OCCURRENCE Found in a 32-year-old Thai male blood donor OTHER INFORMATION Quantity in the heterozygote 28% REFERENCES 1. Pootrakul, S., Boonyarat, D., Kematorn, B., Suanpan, S., and Wasi, P.: Hemoglobin, 1:781, 1977. Hb Shaare Zedek alpha56(E5)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS This fast-moving variant separates from Hb A at alkaline pH; moves to the position of Hb H on paper and cellulose acetate CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in six members of a Jewish family OTHER INFORMATION Quantity in heterozygotes not clearly determined; some members of this family may have an interacting alpha-thal REFERENCES 1. Abramov, A., Lehmann, H., and Robb, L.: FEBS Lett., 113:235, 1980. Hb Belliard alpha56(E5)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Cellulose acetate (alkaline pH) shows an abnormal band that migrated towards the anode CHROMATOGRAPHY Hb A and Hb X can be separated by anion exchange HPLC STRUCTURE STUDIES The variant was identified by separating the tryptic peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAT or AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Not reported OCCURRENCE Found in a family from Spain OTHER INFORMATION Quantity in heterozygotes about 25% REFERENCES 1. Wajcman, H., Gombaud-Saintonge, G., Galacteros, F., Martha, M., and Vertongen, F.: Hemoglobin, 13:157, 1989. Hb Port Huron alpha56(E5)Lys->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation observed CHROMATOGRAPHY No separation observed; the electrophortetic pattern of the Hb of the carrier was consistent with that of an Hb E heterozygote STRUCTURE STUDIES The tryptic peptides were separated by reversed phase HPLC and their amino acid composition determined DNA ANALYSES Limited to an Nla IV digestion of a PCR obtained alpha gene fragment that gave two specific fragments due to an AAG-> AGG mutation at codon 56; the mutated gene (alpha2 or alpha1) was not defined FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in an African-American family OTHER INFORMATION Some members were heterozygous for Hb E [beta26(B8)Glu-> Lys) and the discovery of the additional alpha-Port Huron mutation was accidental REFERENCES 1. Zwerdling, T., Williams, S., Nasr, S.A., and Rucknagel, D.L.: Hemoglobin, 15: 381, 1991. Hb L-Persian Gulf alpha57(E6)Gly->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS The slowly-moving variant separates from Hb A at alkaline pH; the two Hbs do not separate at low pH; Hb X moves between Hb S and Hb G on starch gel and paper CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a female living near the Persian Gulf OTHER INFORMATION Quantity in the heterozygote about 18% REFERENCES 1. Rahbar, S., Kinderlerer, J.L., and Lehmann, H.: Acta Haematol., 42:169, 1969. Hb J-Norfolk alpha57(E6)Gly->Asp ALSO KNOWN AS Kagoshima; Nishik-I; Nishik-II; Nishik-III CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on starch gel and cellulose acetate at alkaline pH; moves with Hb A (citrate agar) and ahead of Hb A on paper CHROMATOGRAPHY Hb X can be separated from Hb A by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing of selected peptides DNA ANALYSES Not reported; presumed mutation GGC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in English, Italian, Japanese, and Nepali families OTHER INFORMATION Quantity in heterozygotes around 25% REFERENCES 1. Ager, J.A.M., Lehmann, H., and Vella, F.: Br. Med. J., ii:539, 1958. 2. Baglioni, C.: J. Biol. Chem., 237:69, 1962. 3. Imamura, T., Am. J. Hum. Genet., 18:584, 1966. 4. Mehrotra, T.N., Gupta, S.C., Sinha, R., Lehmann, H., and Wiltshire, B.G.: Humangenetik, 27:347, 1975. Hb M-Boston alpha58(E7)His->Tyr ALSO KNOWN AS M-Osaka; M-Gothenburg; M-Kiskunhalas; M-Norin CONTACT Distal histidine; heme contact HEMATOLOGY Cyanosis in the heterozygote; normal hematology ELECTROPHORESIS Hb X and Hb A can be separated at alkaline and acidic pH; Hb X moves slower than Hb A on agar gel and moves as Hb A on paper and starch gel; best separation by IEF CHROMATOGRAPHY Hb X was isolated on an Amberlite CG-50 column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Decreased oxygen affinity; no Bohr effect; decreased cooperativity STABILITY Normal OCCURRENCE Found in German, Swedish, Dutch, Hungarian, and Japanese families OTHER INFORMATION Quantity in heterozygotes 20-30% REFERENCES 1. Gerald, P.S. and Efron, M.L.: Proc. Natl. Acad. Sci. USA, 47:1758, 1961. 2. Pulsinelli, P.D., Perutz, M.F., and Nagel, R.L.: Proc. Natl. Acad. Sci. USA, 70: 3870, 1973. 3. Nishikura, K., Sugita, Y., Nagai, M., and Yoneyama, Y.: Nature, 254:727, 1975. 4. Takahashi, S., Lin, A.K-L.C., and Ho, C.: Biochemistry, 19:5196, 1980. Hb Tottori alpha59(E8)Gly->Val CONTACT Internal HEMATOLOGY Mild hemolytic anemia in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A at alkaline and acid pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGC->GTC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Unstable OCCURRENCE Found in a Japanese family OTHER INFORMATION Quantity in heterozygotes 10-12% REFERENCES 1. Nakatsuji, T., Miwa, S., Ohba, Y., Miyaji, T., Matsumoto, N., and Matsuoka, I.: Hemoglobin, 5:427, 1981. Hb Adana alpha59(E8)Gly->Asp CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X can be separated from Hb A by IEF; Hb X focuses ahead of Hb A CHROMATOGRAPHY Hb X can be separated from Hb A by cation exchange HPLC STRUCTURE STUDIES See DNA analyses DNA ANALYSES Sequencing of amplified DNA which included the alpha-globin genes identified the variant; a GGC->GAC mutation was observed at codon 59 of the alpha1 gene FUNCTIONAL STUDIES Not reported STABILITY Severely unstable OCCURRENCE Found in a Turkish family OTHER INFORMATION This variant occurred in three children in combination with the -(alpha)20.5 kb alpha-thal-1 deletion; all three had Hb H disease; the quantity of Hb Adana in heterozygotes could not be determined REFERENCES 1. Altay, C., Say, B., Yetgin, S., and Huisman, T.H.J.: Am. J. Hematol., 2:1, 1977. 2. Curuk, M.A., Dimovski, A.J., Baysal, E., Gu, L-H., Kutlar, F., Molchanova, T.P., Webber, B.B., Altay, C., Gurgey, A., and Huisman, T.H.J.: Am. J. Hematol., 44:270, 1993. Hb Zambia alpha60(E9)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Only studied by paper electrophoresis; it moves faster than Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in four unrelated families in Zambia OTHER INFORMATION None REFERENCES 1. Barclay, G.P.T., Charlesworth, D., and Lehmann, H.: Br. Med. J., 4:595, 1969. Hb Dagestan alpha60(E9)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; the variant is fast-moving (position of Hb I on starch gel) CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a female from Dagestan OTHER INFORMATION Quantity in the heterozygote estimated at 30% REFERENCES 1. Spivak, V.A., Molchanova, T.P., Ermakov, N.V., Tokarev, Yu.N., Martinez, G., Szelenyi, Ju., Horanyi, M., Foldi, J., Hollan, S., Kazieva, H., and Shamov, I.A.: Hemoglobin, 5:133, 1981. Hb J-Buda alpha61(E10)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves to the position of Hb J on starch gel CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; glycinamidation; CNBr; chymotrypsin; thermolysin; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a large Hungarian family OTHER INFORMATION Found in combination with Hb G-Pest [alpha74(EF3)Asp->Asn] and Hb A in three individuals (causes erythrocytosis); this family study was the first to offer convincing evidence for the presence of duplicated alpha-globin genes in humans REFERENCES 1. Hollan, S.R., Szelenyi, J.G., Brimhall, B., Duerst, M., Jones, R.T., and Koler, R.D.: Nature, 235:47, 1972. 2. Brimhall, B., Duerst, M., Hollan, S.R., Stenzel, P., Szelenyi, J., and Jones, R.T.: Biochim. Biophys. Acta, 336:344, 1974. Hb J-Anatolia alpha61(E10)Lys->Thr CONTACT External HEMATOLOGY Probably normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A at alkaline pH; starch gel showed a fast-moving band in the region of Hb J and a fast extra Hb A2 band CHROMATOGRAPHY Hb X can be separated from Hb A by anion exchange HPLC STRUCTURE STUDIES Tryptic peptides were isolated by reversed phase HPLC; the alphaXT-9 carried an extra threonine at the amino terminus; amino acid analysis; sequencing DNA ANALYSES Mutation in the alpha2 gene: AAG->ACG at codon 61 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in a Turkish woman OTHER INFORMATION Quantity in the heterozygote 27-28% REFERENCES 1. Giardano, P.C., Fodde, R., Amons, R., Ploem, J.E., and Bernini, L.F.: Hemoglobin, 14:119, 1990. Hb Evans alpha62(E11)Val->Met CONTACT Internal; heme contact HEMATOLOGY Mild hemolytic anemia in the heterozygote ELECTROPHORESIS All electrophoretic methods used failed to detect an abnormal Hb CHROMATOGRAPHY Anion, cation exchange, and reversed phase HPLC failed to indicate the presence of an abnormal Hb STRUCTURE STUDIES Tryptic peptides of a mixture of alphaA+alphaX were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Mutation in the alpha2 gene: GTG->ATG at codon 62 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found as a de novo mutation in a Caucasian female and her daughter OTHER INFORMATION Quantity in heterozygotes could not be determined with certainty; ~10% by heat denaturation REFERENCES 1. Wilson, J.B., Webber, B.B., Kutlar, A., Reese, A.L., McKie, V.C., Lutcher, C.L., Felice, A.E., and Huisman, T.H.J.: Hemoglobin 13:557, 1989. Hb Pontoise alpha63(E12)Ala->Asp ALSO KNOWN AS J-Pontoise CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A at alkaline pH but not at acidic pH; moves faster than Hb A on cellulose acetate CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity, normal Bohr effect, and heme-heme interaction; a normal 2,3-DPG effect STABILITY Mildly unstable OCCURRENCE Found in Spanish families OTHER INFORMATION Quantity in heterozygotes about 12% REFERENCES 1. Thillet, J., Blouquit, Y., Perrone, F., and Rosa, J.: Biochim. Biophys. Acta, 491: 16, 1977. 2. Gonzalez-Redondo, J.M., Wilson, J.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 11:47, 1987. Hb G-Waimanalo alpha64(E13)Asp->Asn ALSO KNOWN AS Aida CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slower than Hb A on starch gel CHROMATOGRAPHY Hb X can be isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting on paper and on a reversed phase HPLC column; amino acid analysis; sequencing DNA ANALYSES Mutation in the alpha2 gene: GAC->AAC at codon 64 (Ref. 6) FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in Filipino, Indian, and Rumanian families OTHER INFORMATION Quantity in heterozygotes 20-22%; found in combination with beta-thal, and with Hb D-Los Angeles REFERENCES 1. Blackwell, R.Q., Jim, R.T.S., Tan, T.G.H., Weng, M-I., Liu, C-S., and Wang, C-L.: Biochim. Biophys. Acta, 322:27, 1973. 2. Bunn, H.F., Altman, A.J., Stangland, K., Firshein, S.I., Forget, B., Schmidt, G.J., and Jones, R.T.: Hemoglobin, 2:531, 1978. 3. Baine, R.M., Wright, J.M., and Wilkinson, R.W.: Hemoglobin, 3:293, 1979. 4. Harano, T., Harano, K., Ueda, S., Shibata, S., and Imai, K.: Hemoglobin, 5:591, 1981. 5. Manca, L., Masala, B., Manca, M., Ferranti, P., and Pucci, P.: Hemoglobin, 18: 53, 1994. 6. Landin, B. and Berg, A.: Hemoglobin, 18:71, 1994. Hb Perspolis alpha64(E13)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline and acidic pH; Hb X moves slightly faster than Hb D on cellulose acetate and starch gel CHROMATOGRAPHY Hb X can be isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in an Indian Sikh OTHER INFORMATION Quantity in the heterozygote 20% REFERENCES 1. Rahbar, S., Ala, F., Akhavan, E., Nowzari, G., Shoa'l, I., and Zamanianpoor, M.H.: Biochim. Biophys. Acta, 427:119, 1976. Hb Q-India alpha64(E13)Asp->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline and acidic pH; Hb X moves to the position of Hb S on paper, starch gel, and cellulose acetate; moves between Hb A and Hb S, as a sharp band closer to Hb A on citrate agar CHROMATOGRAPHY Hb X can be isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Mutation in the alpha1 gene: GAC->CAC at codon 64 (Ref. 3) FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in three Hindu families and in a Canadian family of mixed French and Iranian ancestry OTHER INFORMATION Quantity in heterozygotes ~17%; found in combination with beta-thal REFERENCES 1. Sukumaran, P.K., Merchant, S.M., Desai, M.P., Wiltshire, B.G., and Lehmann, H.: J. Med. Genet., 9:436, 1972. 2. Schmidt, R.M., Ali, M.A.M., Bechtel, K.C., and Moo-Penn, W.F.: Am. J. Clin. Pathol., 66:446, 1976. 3. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Guangzhou-Hangzhou alpha64(E13)Asp->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb A and Hb A2 CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->GGC; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly increased oxygen affinity STABILITY Normal OCCURRENCE Found in two apparently unrelated Chinese families OTHER INFORMATION Quantity in heterozygotes 19-22% REFERENCES 1. Jen, P.C. and Liu, Y.: Hemoglobin, 11:25, 1987. 2. Zhou, Z-Q., Chen, L-C., Chen, P-F., Zhang, K-Q., and Wang, Y-H.: Hemoglobin, 11:31, 1987. Hb G-Philadelphia alpha68(E17)Asn->Lys ALSO KNOWN AS G-Knoxville; Stanleyville-I, D-Washington; D-St. Louis; G-Bristol; G-Azakouli; D-Baltimore CONTACT External HEMATOLOGY No hematological abnormalities in the heterozygote due to the presence of the Hb G-Philadelphia anomaly ELECTROPHORESIS Hb X and Hb A separate at alkaline pH but not at acidic pH; moves to the position of Hb S on paper, starch gel, and cellulose acetate; excellent separation on IEF CHROMATOGRAPHY Hb X separates from Hb A by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or by cation exchange chromatography or by reversed phase HPLC; amino acid analysis DNA ANALYSES Two mutations have been detected (Refs. 9,10); 1) AAC->AAG on a chromosome that carries the 3.7 kb deletion (-alpha3.7/ on the alpha2alpha1 hybrid gene); 2) AAC->AAA of the alpha2 gene of a chromosome with a normal complement of two alpha-globin genes (alphaGalpha/) FUNCTIONAL STUDIES Normal STABILITY Stable OCCURRENCE This is the most common alpha chain variant in Blacks; also present in Italians from Northern Italy and Sardinia, and in a few Chinese families OTHER INFORMATION 1) Hb G-Philadelphia in Blacks is present on a chromosome with the 3.7 kb deletion (alpha-thal-2); the quantity of Hb G in such individuals varies between 30-35%. 2) When an alpha-thal-2 (3.7 kb deletion) occurs in trans (-alphaG/-alpha) the quantity of Hb G is increased to ~45%; these individuals have a distinct microcytosis and hypochromia (alpha-thal-2 homozygotes). 3) Homozygosity for Hb G-Philadelphia (-alphaG/-alphaG) results in 100% G-Philadelphia; these individ-uals also have a distinct microcytosis; hypochromia (alpha-thal-2 homozygotes). 4) Hb G-Philadelphia in combination with an alpha-thal-1, although extremely rare, results in an Hb H disease (-alphaG/--) and 100% G-Philadelphia. 5) The occurrence of Hb G-Philadelphia (-alphaG/alphaalpha) with Hb S and/or Hb C is rather common. 6) Italians with Hb G-Philadelphia have a full complement of four alpha-globin genes (alphaGalpha/alphaalpha) and 20-25% G-Philadelphia; no hematological abnormalities are found REFERENCES 1. Baglioni, C. and Ingram, V.M.: Biochim. Biophys. Acta, 48:253, 1961. 2. Minnich, V., Cordonnier, J.K., Williams, W.J., and Moore, C.V.: Blood, 19:137, 1962. 3. Dance, N., Huehns, E.R., and Shooter, E.M.: Biochim. Biophys. Acta, 86:144, 1964. 4. Chernoff, A.I. and Pettit, N., Jr.: Biochim. Biophys. Acta, 97:47, 1965. 5. Bowman, B., Barnett, D.R., Hodgkinson, K.T., and Schneider, R.G.: Nature, 211:1305, 1966. 6. Blackwell, R.Q., Wang, C.L., Liu, C-S., and Shih, T-B.: Vox Sang., 25:184, 1973. 7. Rucknagel, D.L. and Rising, J.A.: Am. J. Med., 59:53, 1976. 8. Milner, P.F. and Huisman, T.H.J.: Br. J. Haematol., 34:207, 1976. 9. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. 10. Molchanova, T.P., Pobedimskaya, D.D., Ye, Z., and Huisman, T.H.J.: Am. J. Hematol., 45:345, 1994. Hb Ube-2 alpha68(E17)Asn->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; it moves ahead of Hb A on agar gel CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in a few Japanese families OTHER INFORMATION Quantity in heterozygotes 22-23% REFERENCES 1. Miyaji, T., Iuchi, I., Yamamoto, K., Ohba, Y., and Shibata, S.: Clin. Chim. Acta, 16:1967. 2. Imai, K., Morimoto, H., Kotani, M., Shibata, S., Miyaji, T., and Masutomo, K.: Biochim. Biophys. Acta, 200:197, 1970. 3. Iuchi, I., Hidaka, K., Shimasaki, S., and Mizuta, W.: Kawasaki Med. J., 10(1):21, 1984. Hb J-Habana alpha71(E20)Ala->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS This fast-moving variant separates from Hb A at alkaline pH; Hb X moves to the position of Hb J-Baltimore on paper CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a Cuban family and a few Japanese families OTHER INFORMATION Quantity in heterozygotes ~20% REFERENCES 1. Colombo, B., Vidal, H., Kamuzora, H., and Lehmann, H.: Biochim. Biophys. Acta, 351:1, 1974. 2. Ohba, Y., Yoshinaka, H., Hattori, Y., Matsuoka, M., and Miyaji, T.: Hemoglobin, 7:327, 1983. 3. Hidaka, K., Iuchi, I., Shimasaki, S., Mizuta, W., Takatsuka, M., Mori, T., Tohdoh, A., and Matsuo, M.: Hemoglobin, 10:65, 1986. Hb Ozieri alpha71(E20)Ala->Val CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS This silent variant migrates as a band slightly anodal to Hb A and Hb F by IEF with an ultra narrow pH gradient CHROMATOGRAPHY Not reported STRUCTURE STUDIES Hb X was characterized by combining FAB mass spectrometry with electrospray spectrometry DNA ANALYSES Not reported; presumed mutation GCG->GTG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in several unrelated Sardinian newborn babies and their parents OTHER INFORMATION Quantity in adult heterozygotes 27.1 + or - 4.8% REFERENCES 1. Ferranti, P., Parlapiano, A., Malorni, A., Pucci, P., Marino, G., Cossu, G., Manca, L., and Masala, B.: Biochim. Biophys. Acta, 1162:203, 1993. Hb Daneskgah-Tehran alpha72(EF1)His->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on cellulose acetate and starch gel at alkaline pH; Hb X moves with Hb A on agar gel at pH 6.2 CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in an Iranian and an Argentinean family OTHER INFORMATION Quantity in heterozygotes 25% REFERENCES 1. Rahbar, S., Nowzari, G., and Daneshmond, P.: Nature New Biol., 245:268, 1973. 2. de Weinstein, B.I., Kutlar, A., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 9:409, 1985. Hb Q-Thailand alpha74(EF3)Asp->His ALSO KNOWN AS G-Taichung; Mahidol; Kurashiki; Asabara CONTACT External HEMATOLOGY Mild thalassemic features in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on paper and to the position of Hb G on starch gel and cellulose acetate at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAC->CAC mutation at codon 74 in the alpha1 gene of an alpha-thal-2 chromosome (-4.2 kb) (Ref. 9) FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Normal OCCURRENCE Found in Chinese, Thai, and Japanese families OTHER INFORMATION The Hb Q-Thailand mutation occurs in the alpha1-globin gene on a chromosome with the alpha2-globin gene deleted; the quantity in the heterozygote is therefore a high 30-35% REFERENCES 1. Blackwell, R.Q. and Liu, C-S.: Biochim. Biophys. Acta, 200:70, 1970. 2. Pootrakul, S. and Dixon, G.H.: Can. J. Biochem., 48:1066, 1970. 3. Lorkin, P.A., Charlesworth, D., Lehmann, H., Rahbar, S., Tuchinda, S., and Lie-Injo, L.E.: Br. J. Haematol., 19:117, 1970. 4. Iuchi, I., Hidaka, K., Ueda, S., Shibata, S., and Kusumoto, T.: Hemoglobin, 2:79, 1978. 5. Lie-Injo, L.E., Dozy, A.M., Kan, Y.W., Lopes, M., and Todd, D.: Blood, 54:1407, 1979. 6. Higgs, D.R., Hunt, D.M., Drysdale, H.C., Clegg, J.B., Pressley, L., and Weatherall, D.J.: Br. J. Haematol., 46:387, 1980. 7. Beris, P., Huber, P., Miescher, P.A., Wilson, J.B., Kutlar, A., Chen, S.S., and Huisman, T.H.J.: Am. J. Hematol., 24:395, 1987. 8. Chen, S-S., Yang, K-K., Jia, P-C., Liang, C-C., Zhang, M-J., Huang, M-X., Zhang, G-L., Wen, P-C., and Du, S-K.: Hemoglobin, 16:409, 1992. 9. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Lille alpha74(EF3)Asp->Ala CONTACT External; near central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves to the position of Hb S on cellulose acetate CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GCC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in an Algerian female OTHER INFORMATION Quantity in the heterozygote reported as 34% REFERENCES 1. Djoumessi, S., Rousseaux, J., Descamps, J., Goudemand, M., and Dautrevaux, M.: Hemoglobin, 5:475, 1981. Hb G-Pest alpha74(EF3)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on starch gel at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; glycinamindation; CNBr; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a large Hungarian family OTHER INFORMATION Found in combination with Hb J-Buda [alpha61(E10)Lys->Asn] and Hb A in the same individual; quantity in the heterozygote 23%; this study was the first to provide definitive information regarding the duplication of the alpha gene locus REFERENCES 1. Hollan, S.R., Szelenyi, J.G., Brimhall, B., Duerst, M., Jones, R.T., Koler, R.D., and Stocklen, Z.: Nature, 235:47, 1972. 2. Brimhall, B., Duerst, M., Hollan, S.R., Stenzel, P., Szelenyi, J., and Jones, R.T.: Biochim. Biophys. Acta, 336:344, 1974. Hb Chapel Hill alpha74(EF3)Asp->Gly CONTACT External; near central cavity HEMATOLOGY Uncertain, may cause mild anemia in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on starch gel at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange HPLC; amino acid analysis; sequencing DNA ANALYSES A GAC->GGC mutation at codon 74 of the alpha1-globin gene (Ref. 3) FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a Caucasian female and in a Chinese family OTHER INFORMATION Quantity in heterozygotes 20-25% REFERENCES 1. Orringer, E.P., Wilson, J.B., and Huisman, T.H.J.: FEBS Lett., 65:297, 1976. 2. Liang, H., Lung, Q-F., Tang, Z., Fei, Y-J., Su, C., Chen, S.S., Webber, B.B., Wilson, J.B., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 10:77, 1986. 3. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Q-Iran alpha75(EF4)Asp->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S at alkaline pH CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->CAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Stable OCCURRENCE Found in a few Iranian and Turkish families OTHER INFORMATION Quantity in the heterozygote 17-19% REFERENCES 1. Lorkin, P.A., Charlesworth, D., Lehmann, H., Rahbar, S., Tuchinda, S., and Lie-Injo, L.E.: Br. J. Haematol., 19:117, 1970. 2. Lie-Injo, L.E., Dozy, A.M., Kan, Y.W., Lopes, M., and Todd, D.: Blood, 54:1407, 1979. 3. Aksoy, M., Gurgey, A., Altay, C., Kilinc, Y., Carstairs, K.C., Kutlar, A., Chen, S.S., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 10:215, 1986. Hb Duan alpha75(EF4)Asp->Ala CONTACT External HEMATOLOGY Mild microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb F on cellulose acetate at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAC->GCC mutation at codon 75 of the alpha1 gene on a chromosome with the 4.2 kb deletion that removes the alpha2 gene FUNCTIONAL STUDIES Not reported STABILITY Stable OCCURRENCE Found in a few Chinese families OTHER INFORMATION Quantity in heterozygotes ~37%; this high level is due to the additional alpha-thal-2 (4.2 kb) deletion REFERENCES 1. Liang, C-C., Chen, S-S., Jia, P-C., Wang, L-F., Luo, H-Y., Liu, G-Y., Liang, S., Lung, G-F., Yu, C-M., Zhuang, L-Z., Liang, B-L., and Tang, Z-N.: Hemoglobin, 5:481, 1981. 2. Liang, S., Tang, Z., Su, C., Lung, Q., Liang, R., Fei, Y.J., Kutlar, F., Wilson, J.B., Webber, B.B., Hu, H., and Huisman, T.H.J.: Hemoglobin, 12:13, 1988. Hb Winnipeg alpha75(EF4)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb A on paper and starch gel; moves between Hb S and Hb F on cellulose acetate and like Hb A on citrate agar CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a few Caucasian families in Canada and the United States OTHER INFORMATION Quantity in heterozygotes 13-20% REFERENCES 1. Vella, F., Wiltshire, B., Lehmann, H., and Galbraith, P., Clin. Biochem., 6:66, 1973. 2. Nakatsuji, T., Abraham, B.L., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 7:105, 1983. Hb Matsue-Oki alpha75(EF4)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves like Hb S on cellulose acetate and starch gel at alkaline pH; slightly slower than Hb A at acidic pH on citrate agar CHROMATOGRAPHY Hb A and Hb X can be separated by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Normal OCCURRENCE Found in a few Japanese and Black families OTHER INFORMATION Quantity in heterozygotes 12-24%; Hb M-O occurred in one Black family together with Hb G-Philadelphia [alpha68(E17)Asn->Lys] that is linked to alpha-thal-2 (-3.7 kb). In one child both alpha chain variants (plus an alpha-thal-2 heterozygosity) and Hb A occurred together; this is a second observation of two alpha chain variants and normal alphaA in one individual, again supporting duplication of the alpha locus. The quantities in this child were 58% Hb G + Hb M-O and 42% Hb A (Ref. 3). REFERENCES 1. Ohba, Y., Miyaji, T., Matsuoka, M., Takeda, I., Fukuba, Y., Shibata, S., and Ohkura, K.: Hemoglobin, 1:383, 1977. 2. Moo-Penn, W.F., Johnson, M.H., and Therrell, B.L., Jr.: Hemoglobin, 2:71, 1978. 3. Zeng, Y-T., Headlee, M.E., Henson, J., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Biochim. Biophys. Acta, 707:206, 1982. Hb Mizushi alpha75(EF4)Asp->Gly CONTACT External; near central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->GGC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Normal OCCURRENCE Found in a Japanese family OTHER INFORMATION Quantity in heterozygotes ~14% REFERENCES 1. Iuchi, I., Shimasaki, S., Hidaka, K., Harano, T., Ueda, S., Shibata, S., Mizushima, J., and Kubo, N.: Hemoglobin, 4:209, 1980. Hb Noko alpha76(EF5)Met->Lys CONTACT Internal DNA ANALYSES Not reported; presumed mutation ATG->AAG; alpha2 or alpha1 OTHER INFORMATION This variant was reported in a list of hemoglobinopathies from Japan (dated 1981); no details have been presented REFERENCES 1. Shibata, S., Ueda, S., Miyaji, T., and Imamura, T.: Hemoglobin, 5:509, 1981. Hb Aztec alpha76(EF5)Met->Thr CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation observed at alkaline and acidic pH CHROMATOGRAPHY Hb X and Hb A apparently do not separate by cation or anion exchange HPLC; the variant was detected as an abnormal alpha chain by reversed phase HPLC STRUCTURE STUDIES Tryptic peptides were separated by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation ATG->ACG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Not reported OCCURRENCE Found in a newborn and her mother of native Mexican and Spanish descent OTHER INFORMATION None REFERENCES 1. Shelton, J.B., Shelton, J.R., Schroeder, W.A., and Powars, D.R: Hemoglobin, 9:325, 1985. Hb GuiZhou alpha77(EF6)Pro->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X has a mobility like Hb G on cellulose acetate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Separation of tryptic peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 47-year-old Chinese woman of the Miao ethnic group and four members of her family OTHER INFORMATION Quantity in the heterozygote ~25% REFERENCES 1. Chih-chuan, L., Fei, X., Kegong, Y., Songsen, C., Peichen, J., Maoqi, Z., and Zhiheng, Z.: Hemoglobin, 8:387, 1984. Hb Stanleyville-II alpha78(EF7)Asn->Lys CONTACT External HEMATOLOGY Normal in heterozygotes ELECTROPHORESIS Hb X moves as Hb S on starch block, paper, starch gel, and cellulose acetate at alkaline pH; Hb X moves with Hb A on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->AAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in Black families from the Congo, Uganda, Zaire, Texas (USA), and Alsace (France) OTHER INFORMATION Quantity in heterozygotes ~24%; in combination with Hb S it forms a hybrid Hb (alpha2St-IIbeta2S) which in contrast to normal Hb S (alpha2beta2S) does not readily sickle or form fibers (Ref. 5) REFERENCES 1. Dherte, P., Vandepitte, J., Ager, J.A.M., and Lehmann, H.: Br. Med. J., ii:282, 1959. 2. Schneider, R.G. and Haggard, M.E.: Br. Med. J., ii:285, 1959. 3. Van Ros, G., Beale, D., and Lehmann, H.: Br. Med. J., 4:92, 1968. 4. North, M.L., Darbre, P.D., Lehmann, H., and Juif, J.G.: Acta Haematol., 53:56, 1975. 5. Rhoda, M-D., Martin, J., Blouquit, Y., Garel, M-C., Edelstein, S.J., and Rosa, J.: Biochem. Biophys. Res. Commun., 111:8, 1983. Hb J-Singa alpha78(EF7)Asn->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS The fast-moving Hb X separates from Hb A at alkaline pH CHROMATOGRAPHY Hb X and Hb A were separated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic peptides were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a French-Acadian family living in Canada OTHER INFORMATION Quantity in the heterozygote 25-32% (alpha-thal-2 was not excluded) REFERENCES 1. Wong, S.C., Ali, M.A.M., Pond, J.R., Rubin, S.M., Johnson, S.E.N., Wilson, J.B., and Huisman, T.H.J.: Biochim. Biophys. Acta, 784:187, 1984. Hb Davenport alpha78(EF7)Asn->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb F on IEF CHROMATOGRAPHY Separation was obtained by cation exchange HPLC STRUCTURE STUDIES Tryptic peptides were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES An AAC->CAC mutation at codon 78 in the alpha1 gene (Ref. 2) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Caucasian family of German descent OTHER INFORMATION Quantity in heterozygotes 19.5-21% REFERENCES 1. Wilson, J.B., Webber, B.B., Plaseska, D., de Alarcon, P.A., McMillan, S.K., and Huisman, T.H.J.: Hemoglobin, 14:599, 1990. 2. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Mantes-La-Jolie alpha79(EF8)Ala->Thr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Variant was detected by IEF; it focuses very close to Hb A CHROMATOGRAPHY No separation reported by cation exchange HPLC; the alphaX chain elutes ahead of alphaA by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of (AE) alphaA+alphaX chains; separation of peptides by HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->ACC; alpha2 or alpha1 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in members of a family from Chad, North Central Africa OTHER INFORMATION Quantity alphaX ~20% of total alpha REFERENCES 1. Wajcman, H., Blouquit, Y., Lahary, A., Soummer, A.M., Groff, P., Bardakdjian, J., Prehu, C., Riou, J., Godard, C., and Galacteros, F.: Hemoglobin, 19:281, 1995. Hb Ann Arbor alpha80(F1)Leu->Arg CONTACT External HEMATOLOGY Normal in the heterozygote; when associated with alpha-thal: hemolytic anemia, hypochromia, microcytosis, target cells, and reticulocytosis ELECTROPHORESIS Hb X moves slower than Hb S on starch gel at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a Caucasian family OTHER INFORMATION Quantity in heterozygotes 2-5%, and 10-15% when in combination with alpha-thal; there is evidence that the alphaX chain is rapidly catabolized REFERENCES 1. Rucknagel, D.L., Brandt, N.J., and Spencer, H.H.: In Genetical, Functional and Physical Studies of Hemoglobin, edited by T. Arends, G. Bemski, and R. Nagel, Karger AG, Basel, 1971. 2. Adams, J.G., III, Winter, W.P., Rucknagel, D.L., and Spencer, H.H.: Science, 176:1427, 1972. Hb Nigeria alpha81(F2)Ser->Cys CONTACT External HEMATOLOGY Unknown for a heterozygote; the subject with the variant had microcytosis, hypochromia, and a low level of Hb S (29%) ELECTROPHORESIS The variants (alpha2Xbeta2 and alpha2Xbeta2S) move slightly faster than Hb A and Hb S at alkaline pH CHROMATOGRAPHY Partial separation of the two major variants (alpha2Xbeta2 and alpha2Xbeta2S) from Hb A and Hb S on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by column chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TCC->TGC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Normal OCCURRENCE Observed in a Nigerian female with a compound heterozygosity for Hb S and Hb Nigeria, and an alpha-thal-2 homozygosity OTHER INFORMATION The quantity of the alphaX containing Hb in this female was estimated between 40 and 48% REFERENCES 1. Honig, G.R., Shamsuddin, M., Tremaine, L.M., Mason, R.G., Vida, L.N., Sarnwick, R., and Shahidi, N.T.: Blood, 52:113a (Suppl. 1), 1978. 2. Honig, G.R., Shamsuddin, M., Mason, R.G., Vida, L.N., Tremaine, L.M., Tarr, G.E., and Shahidi, N.T.: Blood, 55:131, 1980. Hb Garden State alpha82(F3)Ala->Asp CONTACT Internal DNA ANALYSES Not reported; presumed mutation GCC->GAC; alpha2 or alpha1 OTHER INFORMATION This variant was reported in an abstract that appeared in 1978; no details as to its properties have been published REFERENCES 1. Winter, W.P., Rucknagel, D.L., and Fielding, J.: Clin. Res., 26:22A, 1978. Hb Etobicoke alpha84(F5)Ser->Arg CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S (starch gel) at alkaline pH but not at acidic pH (agar gel) CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGC->AGG or CGC or AGA; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Unstable OCCURRENCE Found in a Canadian family of Northern Irish ancestry and in a newborn male of French-Cherokee Indian-English descent OTHER INFORMATION Quantity in the heterozygote 15-20% REFERENCES 1. Crookston, J.H., Farquharson, H.A., Beale, D., and Lehmann, H.: Can. J. Biochem., 47: 143, 1969. 2. Headlee, M.G., Nakatsuji, T., Lam, H., Wrightstone, R.N., and Huisman, T.H.J.: Hemoglobin, 7:285, 1983. Hb G-Norfolk alpha85(F6)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves just ahead of Hb S at alkaline pH; moves with Hb A on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a few English families in England and Canada OTHER INFORMATION Quantity in heterozygotes 18-23% REFERENCES 1. Huntsman, R.G., Hall, M., Lehmann, H., and Sukumaran, P.K.: Br. Med. J., i:720, 1963. 2. Lorkin, P.A., Huntsman, R.G., Ager, J.A.M., Lehmann, H., Vella, F., and Darbre, P.D.: Biochim. Biophys. Acta, 379:22, 1975. 3. Cohen-Solal, M., Manasse, B., Thillet, J., and Rosa, J.: FEBS Lett., 50:163, 1975. Hb Atago alpha85(F6)Asp->Tyr CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb X moves slower than Hb F on starch gel at alkaline pH CHROMATOGRAPHY The variant was isolated on a CM-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Not reported OCCURRENCE Found in a Japanese female OTHER INFORMATION Quantity in the heterozygote 22-24% REFERENCES 1. Fujiwara, N., Maekawa, T., and Matsuda, G.: Int. J. Prot. Res., 3:35, 1971. Hb Inkster alpha85(F6)Asp->Val CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on cellulose acetate at alkaline pH but like Hb A on citrate agar at acidic pH CHROMATOGRAPHY Isolated on a DEAE-Sephadex or DEAE-cellulose column; good separation by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; cation exchange chromatography; amino acid analysis DNA ANALYSES A GAC->GTC mutation at codon 85 in the alpha2 gene (Ref. 2) FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Stable OCCURRENCE Found in an English-German family and in some Black families OTHER INFORMATION Quantity in the heterozygote 21-23%; found in association with beta-thal REFERENCES 1. Reed, R.E., Winter, W.P., and Rucknagel, D.L.: Br. J. Haematol., 26:475, 1974. 2. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J., Br. J. Haematol., 88:300, 1994. Hb Moabit alpha86(F7)Leu->Arg CONTACT Heme contact HEMATOLOGY Mild hemolytic anemia in the heterozygote; reticulocytosis ELECTROPHORESIS Hb X moves slightly faster than Hb S on starch block at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG; alpha2 or alpha1 FUNCTIONAL STUDIES Decreased oxygen affinity STABILITY Unstable; the Leu->Arg replacement occurs next to the heme binding proximal histidine, greatly affecting the stability of the protein OCCURRENCE Found in a Turkish male OTHER INFORMATION Quantity in the heterozygote was estimated at about ~15% REFERENCES 1. Knuth, A., Pribilla, W., Marti, H.R., and Winterhalter, K.H.: Acta Haematol., 61: 121, 1979. Hb Iwata alpha87(F8)His->Arg CONTACT Heme contact; proximal histidine HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A on starch gel and cellulose acetate at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DE-52 cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in Japanese and Chinese families OTHER INFORMATION Quantity in heterozygotes 5-10%; abnormal spectrum of oxy-Hb; spectrum of cyan-ferriHb is normal; variant carries two heme groups/tetramer REFERENCES 1. Ohba, Y., Miyaji, T., Hattori, Y., Fuyuno, K., and Matsuoka, M.: Hemoglobin, 4: 307, 1980. 2. Liu, G-Y., Zhang, G-X., Nie, S-Y., Luo, H-Y., Teng, Y-Q., Liu, S-P., Song, M., Son, L., Chen, S-S., Jia, P-C., and Liang, C-C.: Hemoglobin, 7:279, 1983. Hb M-Iwate alpha87(F8)His->Tyr ALSO KNOWN AS M-Kankakee; M-Oldenburg; M-Sendai CONTACT Heme contact; proximal histidine HEMATOLOGY Cyanosis ELECTROPHORESIS Separation of Hb X and Hb A is possible at alkaline pH; Hb X appears as a grayish-green band; best results are obtained with IEF CHROMATOGRAPHY Can be isolated on columns with different cation or anion exchange material STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; cation exchange chromatography; amino acid analysis DNA ANALYSES A CAC->TAC mutation at codon 87 of the alpha1 gene (Ref. 15) FUNCTIONAL STUDIES Decreased oxygen affinity; normal Bohr effect between pH values 6.3-7.5 STABILITY Relatively stable OCCURRENCE Found in Japanese, Irish, German, Turkish, Rumanian, Scottish- German, and Black families; the occurrence of this variant in some families is the result of a spontaneous mutation OTHER INFORMATION Quantity in heterozygotes 15-25%; ferriHb (metHb), responsible for the cyanotic appearance of the carrier, already observed at birth; specific spectral changes REFERENCES 1. Shibata, S., Tamura, A., Iuchi, I., and Takahashi, H.: Acta Haematol. Jap., 23:96, 1960. 2. Heller, P., Weinstein, H.G., Yakulis, V.J., and Rosenthal, I.M.; Nature, 210:1182, 1962. 3. Tonz, V.O., Simon, H.A., and Hasselfeld, W.: Schweiz. Med. Wochenschr., 92: 1311, 1962. 4. Miyaji, T., Iuchi, I., Shibata, S., Takeda, I., and Tamura, A.: Acta Haematol. Jap., 26:538, 1963. 5. Kikuchi, G., Hayashi, N., and Tamura, A.: Biochim. Biophys. Acta, 90:199, 1964. 6. Konigsberg, W. and Lehmann, H.: Biochim. Biophys. Acta, 107:266, 1965. 7. Jones, R.T., Coleman, R.D., and Heller, P.: J. Biol. Chem., 241:2137, 1966. 8. Pik, C. and Tonz, O.: Nature, 210:1182, 1966. 9. Bratu, V., Predescu, C., Lehmann, H., and Charlesworth, D.: Rev. Roum. Med. Int., 8:279, 1971. 10. Ozsoylu, S.: Acta Haematol., 47:225, 1972. 11. Trittelvitz, E., Gersonde, K., and Winterhalter, K.H.: Eur. J. Biochem., 51:33, 1975. 12. Steffens, G., Steffens, G., and Buse, G.: Hoppe-Seyler's Z. Physiol. Chem., 358: 35, 1977. 13. Hesseling, P.B.: South Afr. Med. J., 56:1008, 1979. 14. Mayne, E.E., Elder, G.E., Lappin, T.R.J., and Ferguson, L.A.K.: Hemoglobin, 10: 205, 1986. 15. Horst, J., Assum, G., Griese, E.U., Eigel, A., Hampl, W., and Kohne, E., Hum. Genet., 75:53, 1987. Hb Loire alpha88(F9)Ala->Ser CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by routine electropho-retic methods; it focuses between Hb A and Hb F (near Hb F) on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Hb X was isolated by preparative IEF; the alphaX and beta chains were separated by CM-cellulose chromatography; the tryptic peptides were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCG->TCG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY More stable than Hb A OCCURRENCE Found in a family of Algerian-French descent OTHER INFORMATION Quantity in heterozygotes 25-30% REFERENCES 1. Baklouti, F., Baudin-Chich, V., Kister, J., Marden, M., Teyssier, G., Poyart, C., Delaunay, J., and Wajcman, H.: Eur. J. Biochem., 177:307, 1988. Hb Columbia Missouri alpha88(F9)Ala->Val CONTACT Internal HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation observed by conventional methods or IEF CHROMATOGRAPHY No separation observed; analytic HPLC of the globin chains indicated a broadening of the alpha peak; an abnormal alphaX chain was observed by reversed phase HPLC STRUCTURE STUDIES Tryptic peptides of alphaX chain were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCG->GTG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Not reported OCCURRENCE Found in a Caucasian family OTHER INFORMATION Quantity of the variant in the heterozygote could not be determined REFERENCES 1. Perry, M.C., Head, C., Fairbanks, V.F., Jones, R.T., Taylor, H., and Proud, V.: Mayo Clin. Proc., 66:5, 1991. Hb Valparaiso alpha88(F9)Ala->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X focuses at a pI slightly higher than Hb A and migrates between Hb A and Hb F on cellulose acetate; Hb X and Hb A can be separated by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Hb X was isolated by preparative IEF and digested with trypsin; tryptic peptides were separated by reversed phase HPLC; amino acid analysis; peptide alphaXT-9 was digested with protease V8 DNA ANALYSES Not reported; presumed mutation GCG->GGG; alpha2 or alpha1 FUNCTIONAL STUDIES Slight increase in oxygen affinity STABILITY Not reported OCCURRENCE Found in members of a Chilean family OTHER INFORMATION Quantity in the heterozygote ~27% REFERENCES 1. Wajcman, H., de Montalembert, M., Girot, R., Kister, J., Maier-Redelsperger, M., and Galacteros, F.: Hemoglobin, 18:275, 1994. Hb Luton alpha89(FG1)His->Leu CONTACT External HEMATOLOGY Erythrocytosis and microcytosis in the heterozygote, who is also heterozygous for the alpha-thal-2 4.2 kb deletion ELECTROPHORESIS Two abnormal bands were detected by IEF; Hb X did not separate from Hb A on cellulose acetate (pH 8.6) but resolved as a band cathodal to Hb A on agar gel CHROMATOGRAPHY Not reported STRUCTURE STUDIES The alphaX and alphaA chains were separated by reversed phase HPLC; tryptic peptides of the alphaX chain were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CTC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in members of a Pakistani family OTHER INFORMATION The quantity of Hb X was about ~33% in the heterozygote with an alpha-thal-2 trait REFERENCES 1. Williamson, D., Langdown, J.V., Myles, T., Mason, C., Henthorn, J.S., and Davies, S.C.: Br. J. Haematol., 82:621, 1992. Hb J-Broussais alpha90(FG2)Lys->Asn ALSO KNOWN AS Tagawa-I CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on paper and starch gel at alkaline but not at acidic pH; Hb X and Hb A do not separate on agar gel; it moves like Hb A on citrate agar CHROMATOGRAPHY Hb A and Hb X can be separated by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES An AAG->AAT mutation was observed at codon 90 of the alpha2 gene; an AAG->AAC mutation has also been found at codon 90 of the alpha1 gene (Ref. 6) FUNCTIONAL STUDIES Normal oxygen affinity STABILITY Stable OCCURRENCE Found in French, French-Canadian, Australian, and Japanese families OTHER INFORMATION Quantity in the heterozygote: 24-25% for the alpha2 mutation; 20.5% for the alpha1 mutation REFERENCES 1. De Traverse, P.M., Lehmann, H., Coquelet, M.L., Beale, D., and Isaacs, W.A.: Compt. R. Sceanc. Soc. Biol., 160:2270, 1966. 2. Yanase, T., Hanada, M., Seita, M., Ohya, I., Ohta, Y., Imamura, T., Fujimura, T., Kawasaki, K., and Yamaoka, K.: Jpn. J. Hum. Genet., 13:40, 1968. 3. Vella, F., Charlesworth, D., Lorkin, P.A., and Lehmann, H.: Can. J. Biochem., 48:908, 1970. 4. Braconnier, F., Cohen-Solal, M., Schlegel, N., Blouquit, Y., Thillet, J., Cassius de Linval, J., and Rosa, J.: Nouv. Rev. Fr. d'Hematol., 15:333, 1975. 5. Fleming, P.J., Arnold, B.J., Thompson, E.O.P., Hughes, W.G., and Morgan, L.: Pathology, 10:317, 1978. 6. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb J-Rajappen alpha90(FG2)Lys->Thr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J at alkaline pH CHROMATOGRAPHY Hb A and Hb X separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; reversed phase HPLC; amino acid analysis; DNA sequencing DNA ANALYSES An AAG->ACG mutation at codon 90 in the alpha1-globin gene (Ref. 2) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in members of Indian families OTHER INFORMATION Quantity in the heterozygote 19.5-20.5% (Ref. 2) REFERENCES 1. Hyde, R.D., Kinderlerer, J.L., Lehmann, H., and Hall, M.D.: Biochim. Biophys. Acta, 243: 515, 1971. 2. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Handa alpha90(FG2)Lys->Met ALSO KNOWN AS Munakata CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves ahead of Hb A on starch gel at alkaline pH; moves anodally to Hb A on IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ATG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Normal OCCURRENCE Found in Japanese families OTHER INFORMATION Quantity in the heterozygote 17-19% REFERENCES 1. Harano, T., Harano, K., Shibata, S., Ueda, S., Imai, K., and Seki, M.: Hemoglobin, 6:379, 1982. 2. Sugihara, J., Imamura, T., Kagimoto, M., Matsuo, T., Yamada, H., Imoto, T., and Yanase, T.: Biochim. Biophys. Acta, 744:119, 1983. 3. Hidaka, K., Iuchi, I., Shimasaki, S., Mizuta, W., Takatsuka, M., Mori, T., Tohdoh, A., and Matsuo, M.: Hemoglobin, 10:65, 1986. Hb Port Phillip alpha91(FG3)Leu->Pro CONTACT Heme and alpha1beta2 contacts HEMATOLOGY Mild anemia; reticulocytosis in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb F on starch gel at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate incompletely on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTT->CCT; alpha2 or alpha1T FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a Chinese female OTHER INFORMATION Quantity in the heterozygote about 7% REFERENCES 1. Brennan, S.O., Tauro, G.P., Melrose, W., and Carrell, R.W.: FEBS Lett., 81:115, 1977. Hb J-Cape Town alpha92(FG4)Arg->Gln CONTACT alpha1beta2 contact HEMATOLOGY Mild erythrocytosis and microcytosis in the heterozygote ELECTROPHORESIS Hb A moves to the position of Hb J at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; reversed phase HPLC; amino acid analysis DNA ANALYSES A CGG->CAG mutation at codon 92 of the alpha2alpha1 hybrid gene that remains on a chromosome with the 3.7 kb deletion (Ref. 7) FUNCTIONAL STUDIES Increased oxygen affinity; normal Bohr effect; decreased cooperativity STABILITY Normal OCCURRENCE Found in several, partially native, families living in South Africa OTHER INFORMATION Quantity in heterozygotes ~23% (Ref. 7); also found in combination with Hb E, and in a homozygote REFERENCES 1. Botha, M.C., Beale, D., Isaacs, W.A., and Lehmann, H.: Nature, 212:792, 1966. 2. Lines, J.G. and McIntosh, R.: Nature, 215:297, 1967. 3. Ogawa, S., Shulman, R.G., Kynoch, P.A.M., and Lehmann, H.: Nature, 225:1042, 1970. 4. Charache, S. and Jenkins, T.: J. Clin. Invest., 50:1554, 1971. 5. Nagel, R.L., Gibson, Q.H., and Jenkins, T.: J. Mol. Biol., 58:171. 6. Botha, M.C., Stathopoulou, R., Lehmann, H., Rees, J.S., and Plowman, D.: FEBS Lett., 96:331, 1978. 7. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Cemenelum alpha92(FG4)Arg->Trp CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X separates from Hb A by preparative flat-bed IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; ion spray mass spectrometry DNA ANALYSES Not reported; presumed mutation CGG->TGG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Not reported OCCURRENCE Found in a French Caucasian woman OTHER INFORMATION None REFERENCES 1. Kister, J., Soummer, A.M., M'Rad, A., Bohn, B., Prome, Cappellino, B., Chambon, P., Wajcman, H., and Galacteros, F.: Abstract, Journees Scientifique du Club de L'Hemoglobine, Strasbourg, France, June, 1993. Hb Chesapeake alpha92(FG4)Arg->Leu CONTACT alpha1beta2 contact HEMATOLOGY (Mild) erythrocytosis in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on starch gel at alkaline pH but not on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A are readily separated by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CGG->CTG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect; 2,3-DPG and IHP partially restore cooperativity STABILITY Slightly unstable OCCURRENCE Found in a German-Irish family and in a Japanese family OTHER INFORMATION Quantities in heterozygotes 20-35% REFERENCES 1. Clegg, J.B., Naughton, M.A., and Weatherall, D.J.: J. Mol. Biol., 19:91, 1966. 2. Charache, S., Weatherall, D.J., and Clegg, J.B.: J. Clin. Invest., 45:813, 1966. 3. Greer, J.: J. Mol. Biol., 62:241, 1971. 4. Gibson, Q.H. and Nagel, R.L.: J. Biol. Chem., 249:7255, 1974. 5. Imai, K.: J. Biol. Chem., 249:7607, 1974. 6. Jones, C.M., Charache, S., and Hathaway, P.J.: Pediatr. Res., 13:851, 1979. 7. Harano, T., Harano, K., Shibata, S., Ueda, S., Mori, H., and Imai, K.: Hemoglobin, 7:461, 1983. Hb Titusville alpha94(G1)Asp->Asn CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X does not separates from Hb A on paper at alkaline pH but moves as Hb S on starch gel and cellulose acetate at alkaline pH; Hb X separates from Hb A on citrate agar and acid pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity; small Bohr effect STABILITY About normal OCCURRENCE Found in a Black female OTHER INFORMATION Quantity in the heterozygote 35% (subject may have alpha-thal) REFERENCES 1. Schneider, R.G., Atkins, R.J., Hosty, T.S., Tomlin, G., Casey, R., Lehmann, H., Lorkin, P.A., and Nagai, K.: Biochim. Biophys. Acta, 400:365, 1975. Hb Setif alpha94(G1)Asp->Tyr CONTACT alpha1beta2 contact HEMATOLOGY Normal in heterozygotes ELECTROPHORESIS Hb X moves to the position of Hb S on starch gel and cellulose acetate at both alkaline and acidic pH CHROMATOGRAPHY Hb A and Hb X separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography or fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Oxygen affinity about normal; decreased cooperativity STABILITY Unstable OCCURRENCE Found in families from Algeria, Iran, Lebanon, Saudi Arabia, etc. OTHER INFORMATION Quantity in heterozygotes 12-15%; red cells with Hb Setif "sickle" by intracellular crystallization of insoluble Hb REFERENCES 1. Wajcman, H., Belkhodja, O., and Labie, D.: FEBS Lett., 27:298, 1972. 2. Debray, J., Krulik, M., Mehaut, M., Benabadji, M., Trabuchet, G., Wajcman, H., Gacon, G., and Labie, D.: Nouv. Rev. Fr. d'Hematol., 14:627, 1974. 3. Nozari, G. and Rahbar, S.: Hemoglobin, 1:289, 1977. 4. Aubert, J-P., Drupt, F., Rousseaux, J., and Loucheux-Lefebvre, M-H.: 84:375, 1977. 5. Raik, E., Powell, E., Fleming, P., and Gordon, S.: Pathology, 15:453, 1983. 6. Al-Awamy, B., Niazi, G.A., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 9:87, 1985. 7. Charache, S., Raik, E., Holtzclaw, D., Hathaway, P.J., Powell, E., and Fleming, P.: Blood, 70:237, 1987. Hb Sunshine Seth alpha94(G1)Asp->His CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly cathodal to Hb S on cellulose acetate; Hb X moves midway between Hb S and Hb C on starch gel at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb A and Hb X can be isolated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAC->CAC mutation at codon 94 of the alpha2 gene (Ref. 2) FUNCTIONAL STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in a few Caucasian families OTHER INFORMATION Quantity in heterozygotes 20-25% REFERENCES 1. Schroeder, W.A., Shelton, J.B., Shelton, J.R., and Powars, D.: Hemoglobin, 3:145, 1979. 2. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Capa alpha94(G1)Asp->Gly CONTACT alpha1beta2 contact HEMATOLOGY Nearly normal in the heterozygote ELECTROPHORESIS Hb X can be detected by IEF where it has a mobility slightly cathodic to Hb S CHROMATOGRAPHY Hb A and Hb X can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Separation of tryptic peptides by reversed phase HPLC methodology; amino acid analysis DNA ANALYSES A GAC->GGC mutation at codon 94 of the alpha1-globin gene FUNCTIONAL STUDIES Decreased oxygen affinity STABILITY Mildly unstable OCCURRENCE Found in members of a Turkish family OTHER INFORMATION Quantity in the heterozygote 14-15% REFERENCES 1. Dincol, G., Dincol, K., Erdem, S., Pobedimskaya, D.D., Molchanova, T.P., Ye, Z., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 18:57, 1994. Hb Roanne alpha94(G1)Asp->Glu CONTACT alpha1beta2 contact HEMATOLOGY No data available; carrier had mild chronic anemia of unknown etiology ELECTROPHORESIS Hb X has a pI intermediate between those for Hb A and Hb F by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Separation of tryptic peptides of alphaA and alphaX chains by reversed phase HPLC; amino acid analysis; electrospray mass spectral analysis DNA ANALYSES Not reported; presumed mutation GAC->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Decreased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a French woman OTHER INFORMATION Quantity in the heterozygote estimated at 20% REFERENCES 1. Kister, J., Kiger, L., Francina, A., Hanny, P., Szymanowicz, A., Blouquit, Y., Prome, D., Galacteros, F., Delaunay, J., and Wajcman, H.: Biochim. Biophys. Acta, 1246:34, 1995. Hb G-Georgia alpha95(G2)Pro->Leu CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb G on starch gel and slightly slower than Hb G on cellulose acetate at alkaline pH CHROMATOGRAPHY Hb X and Hb A can be separated by anion and cation exchange chromatography STRUCTURE STUDIES Tryptic peptides are separated by cation exchange chromatography; amino acid analysis DNA ANALYSES A CCG->CTG mutation at codon 95 of the alpha2-globin gene (Ref. 5) FUNCTIONAL STUDIES Increased oxygen affinity; decreased heme-heme interaction; normal Bohr effect STABILITY Increased dissociation into dimers (oxyHb); tetramers (deoxyHb) OCCURRENCE Found in several Black families and in a Portuguese family OTHER INFORMATION Quantity in heterozygotes 14-16%; found in combination with Hb S; also in combination with alpha-thal REFERENCES 1. Huisman, T.H.J., Adams, H.R., Wilson, J.B., Efremov, G.D., Reynolds, C.A., and Wrightstone, R.N.: Biochim. Biophys. Acta, 200:578, 1970. 2. Smith, L.L., Plese, C.F., Barton, B.P., Charache, S., Wilson, J.B., and Huisman, T.H.J.: J. Biol. Chem., 247:1433, 1972. 3. Wrightstone, R.N., Hubbard, M., and Huisman, T.H.J.: Acta Haematol., 51: 315, 1974. 4. North, M.L., Garel, M.C., Thillet, J., Oberling, Fr., Lang, J.M., Mayer, S., and Rosa, J.: Nouv. Rev. Fr. d'Hematol., 15:460, 1975. 5. Smetanina, N.S., Leonova, J.Y., Levy, N., and Huisman, T.H.J.: Biochim. Biophys. Acta, 1315:188, 1996 Hb Rampa alpha95(G2)Pro->Ser CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly faster than Hb S on starch gel and like Hb S on cellulose acetate at alkaline pH; Hb X does not separate from Hb A on agar gel at acidic pH CHROMATOGRAPHY Hb X and Hb A were separated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CCG->TCG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased heme-heme interaction and Bohr effect STABILITY Dissociation into dimers (oxyHb); tetramers (deoxyHb) OCCURRENCE Found in a few Indian families and in a family of North European ancestry OTHER INFORMATION Quantity in heterozygotes 15% REFERENCES 1. De Jong, W.W.W., Bernini, L.F., and Meera Khan, P.: Biochim. Biophys. Acta, 236:197, 1971. 2. Smith, L.L., Plese, C.L., Barton, B.P., Charache, S., Wilson, J.B., and Huisman, T.H.J.: J. Biol. Chem., 247:1434, 1972. Hb Denmark Hill alpha95(G2)Pro->Ala CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH; best separation with IEF CHROMATOGRAPHY Hb X was isolated by CM-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CCG->GCG; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased heme-heme interaction and Bohr effect STABILITY Not studied in detail OCCURRENCE Found in a West Indian female and a Spanish family OTHER INFORMATION Quantity in heterozygotes 15-19% REFERENCES 1. Wiltshire, B.G., Clark, K.G.A., Lorkin, P.A., and Lehmann, H.: Biochim. Biophys. Acta, 278:459, 1972. 2. Vasseur, C., Francina, A., Wajcman, H., and Galacteros, F.: Hemoglobin, 15: 103, 1991. Hb St. Luke's alpha95(G2)Pro->Arg CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X migrates to the position of Hb S on starch gel at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate by anion and cation exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography and by fingerprinting; amino acid analysis DNA ANALYSES A CCG->CGG mutation at codon 95 of the alpha1 gene (Ref. 4) FUNCTIONAL STUDIES Increased oxygen affinity; decreased heme-heme interaction and Bohr effect STABILITY Increased dissociation (oxyHb); tetramer (deoxyHb) OCCURRENCE Found in Maltese families and in a 72-year-old Japanese male OTHER INFORMATION Quantity in heterozygotes 10-12.5% REFERENCES 1. Bannister, W.H., Grech, J.L., Plese, C.F., Smith, L.L., Barton, B.P., Wilson, J.B., Reynolds, C.A., and Huisman, T.H.J.: Eur. J. Biochem., 29:301, 1972. 2. Lorkin, P.A., Casey, R., Clark, K.G.A., and Lehmann, H.: FEBS Lett., 39:111, 1974. 3. Harano, T., Harano, K., Shibata, S., Ueda, S., Tsuchida, J., Maramoto, K., Yakeishi, Y., and Murakami, T.: Hemoglobin, 7:471, 1983. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Dallas alpha97(G4)Asn->Lys CONTACT Heme contact HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb F on cellulose acetate at alkaline pH; moves slightly anodic to Hb S on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic peptides were separated with an HPLC procedure; amino acid analysis DNA ANALYSES An AAC->AAA mutation at codon 97 of the alpha2 gene (Ref. 2) FUNCTIONAL STUDIES Increased oxygen affinity; normal Bohr, 2,3-DPG, and IHP effects STABILITY Stable OCCURRENCE Found in a few Caucasian families in the Mid-West (USA) OTHER INFORMATION Quantity in heterozygotes 22-23% REFERENCES 1. Dysert, P.A., II, Head, C.G., Shih, T-B., Jones, R.T., and Schneider, R.G.: Blood, 60:53a (Suppl. 1), 1982. 2. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Turriff alpha99(G6)Lys->Glu CONTACT Central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on cellulose acetate at alkaline pH, and migrates midway between Hb A and Hb F on agar gel at pH 6.0; excellent separation on IEF CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC STRUCTURE STUDIES Tryptic peptides of the isolated alpha chains were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found as a de novo mutation in a diabetic woman of Scottish ancestry and her two daughters OTHER INFORMATION Quantity in the heterozygote ~22% REFERENCES 1. Langdown, J.V., Davidson, R.J.L., and Williamson, D.: Hemoglobin, 16:11, 1992. Hb Manitoba alpha102(G9)Ser->Arg CONTACT Central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly anodal to Hb A on starch gel at alkaline pH; Hb X moves as Hb S on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis DNA ANALYSES An AGC->CGC mutation was found in codon 102 of the alpha2 gene; an AGC->AGA mutation was also found in codon 102 of the alpha1 gene (Ref. 4) FUNCTIONAL STUDIES Not reported STABILITY Slightly unstable; decreased dissociation; forms hybrids OCCURRENCE Found in a few British, German-Irish, and Italian families OTHER INFORMATION Quantity in the heterozygote: 19% alpha2 mutant; 24% alpha1 mutant REFERENCES 1. Crookston, J.H., Farquharson, H.A., Kinderlerer, J.L., and Lehmann, H.: Can. J. Biochem., 48:911, 1970. 2. Wrightstone, R.N., Smith, L.L., Wilson, J.B., Vella, F., and Huisman, T.H.J.: Biochim. Biophys. Acta, 412:283, 1975. 3. Sciarratta, G.V., Ivaldi, G, Molaro, G.L., Sansone, G., Salkie, M.L., Wilson, J.B., Reese, A.L., and Huisman, T.H.J.: Hemoglobin, 8:169, 1984. 4. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Contaldo alpha103(G10)His->Arg CONTACT alpha1beta1 contact HEMATOLOGY Moderate hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves like Hb F at alkaline pH, between Hb S and Hb C on citrate agar at acidic pH, and close to Hb F on IEF CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic peptides of the oxidized alphaX chain were separated by reversed phase HPLC; amino acid analysis; sequence analyses of the core peptide DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in an Italian child OTHER INFORMATION Quantity in the heterozygote 15-20% REFERENCES 1. Sciarratta, G.V., Ivaldi, G., Molaro, G.L., Sansone, G., Salkie, M.L., Wilson, J.B., Reese, A.L., and Huisman, T.H.J.: Hemoglobin, 8:169, 1984. Hb Sallanches alpha104(G11)Cys->Tyr CONTACT alpha1beta1 contact HEMATOLOGY Not reported; variant was observed in a French patient with Hb H disease OTHER INFORMATION Identification of the variant was by sequencing of a PCR product of the alpha2 gene; a TGC->TAC mutation was observed at codon 104; no other information is available REFERENCES 1. Morle, F., Francina, A., Philippe, N., Souillet, G., and Godet, J.: Abstract, Journees Scientifiques du Club de L'Hemoglobine, Strasbourg, France, June, 1993. Hb Suan-Dok alpha109(G16)Leu->Arg CONTACT Internal HEMATOLOGY Mild alpha-thal with microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb F at alkaline pH and by IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES A CTG->CGG mutation at codon 109 of the alpha2 gene (Ref. 2) FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a Thai female OTHER INFORMATION Quantity in the heterozygote 8.8%; found in combination with alpha-thal-1 to give Hb H disease REFERENCES 1. Sanguansermsri, T., Matragoon, S., Changloah, L., and Flatz, G.: Hemoglobin, 2:161, 1979. 2. Hundrieser, J., Sanguansermsri, T., Laig, M., Pape, M., Kuhnau, W., and Flatz, G.: Hemoglobin, 14:69, 1990. Hb Petah Tikva alpha110(G17)Ala->Asp CONTACT Internal HEMATOLOGY Near normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH CHROMATOGRAPHY No separation of Hb X and Hb A by DEAE-cellulose or DEAE-Sephadex chromatography STRUCTURE STUDIES The alphaX and alphaA chains separate in CM-cellulose chromatography; tryptic and chymotryptic peptides separated by column chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a few families of Iraqi Jews OTHER INFORMATION Found in combination with alpha-thal-1 to give Hb H disease REFERENCES 1. Honig, G.R., Shamsuddin, M., Zaizov, R., Steinherz, M., Solar, I., and Kirschmann, C.: Blood, 57:705, 1981. Hb Tonosho alpha110(G17)Ala->Thr CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS IEF reveals an abnormal band focusing along the cathodic edge of Hb A CHROMATOGRAPHY Hb X did not separate from Hb A by either cation or anion exchange HPLC STRUCTURE STUDIES Separation of tryptic and chymotryptic peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->ACC; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly increased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a Japanese male and his son OTHER INFORMATION Quantity in the heterozygote about 14% REFERENCES 1. Ohba, Y., Fujisawa, K., Imai, K., Leowattana, W., Tani, Y., Ami, M., and Miyaji, T.: Hemoglobin, 14:413, 1990. Hb Anamosa alpha111(G18)Ala->Val CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X was detected by IEF where it focused just ahead of Hb A CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC STRUCTURE STUDIES Identification by DNA analysis only DNA ANALYSES A GCC->GTC mutation at codon 111 of the alpha2 gene FUNCTIONAL STUDIES Not reported STABILITY Stable OCCURRENCE Discovered in a Caucasian baby and his father OTHER INFORMATION Quantity in the heterozygote ~20% REFERENCES 1. Kazanetz, E.G., Leonova, J.Ye., Wilson, J.B., McMillan, S.K., Walbrecht, M., de Pablos Gallego, J.Ma., and Huisman, T.H.J.: Hemoglobin, 19:1, 1995. Hb Hopkins-II alpha112(G19)His->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly ahead of Hb A at alkaline pH and like Hb A on citrate agar CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Fingerprinting of tryptic and chymotryptic peptides; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->GAC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal in whole blood; increased oxygen affinity in isolated Hb X; decreased heme-heme interaction; normal Bohr effect STABILITY Unstable OCCURRENCE Found in a few Caucasian families OTHER INFORMATION Quantity in heterozygotes 17-27%; found in association with Hb S REFERENCES 1. Charache, S. and Ostertag, W.: Blood, 36:852, 1970. 2. Charache, S., Ostertag, W., and von Ehrenstein, G.: Nature, 234:248, 1971. 3. Clegg, J.B. and Charache, S.: Hemoglobin, 2:85, 1978. Hb Strumica alpha112(G19)His->Arg ALSO KNOWN AS Serbia CONTACT External HEMATOLOGY Nearly normal in the heterozygote; slight hemolysis ELECTROPHORESIS Hb X moves to the position of Hb Lepore at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic and chymotryptic peptides separated by cation exchange chromatography or by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a few Serbian, Turkish, and Macedonian families OTHER INFORMATION Quantity in heterozygotes 16-17% REFERENCES 1. Niazi, G.A., Efremov, G.D., Nikolov, N., Hunter, E., Jr., and Huisman, T.H.J.: Biochim. Biophys. Acta, 412:181, 1975. 2. Beksedic, D., Rajevska, T., Lorkin, P.A., and Lehmann, H.: FEBS Lett., 58: 226, 1975. Hb Twin Peaks alpha113(GH1)Leu->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X can be detected by IEF; it focuses close to Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES The alphaX chain separates from alphaA by CM-cellulose chromatography; tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; digestion of the insoluble core with chymotrypsin HPLC chromatography; sequencing DNA ANALYSES Not reported; presumed mutation CTC->CAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a family of Mexican-Irish descent OTHER INFORMATION Quantity in the heterozygote ~23% REFERENCES 1. Guis, M., Mentzer, W.C., Jue, D.L., Johnson, M.H., McGuffey, J.E., and Moo-Penn, W.F.: Hemoglobin, 9:175, 1985. Hb Chiapas alpha114(GH2)Pro->Arg CONTACT alpha1beta1 contact HEMATOLOGY Not reported ELECTROPHORESIS Hb X is slightly faster than Hb S at alkaline pH CHROMATOGRAPHY Hb X was isolated on an Amberlite IRC-50 column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Mexican family OTHER INFORMATION Quantity in the heterozygote ~25% REFERENCES 1. Jones, R.T., Brimhall, B., and Lisker, R.: Biochim. Biophys. Acta, 154:488, 1968. 2. Ibarra, B., Franco-Gamboa, E., Ramirez, M.L., Cantu, J.M., Wilson, J.B., Lam, H., and Huisman, T.H.J.: Hemoglobin, 5:605, 1981. Hb Nouakchott alpha114(GH2)Pro->Leu CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb F on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES The alphaA and alphaX chains can be separated on an analytical Aquapore RP300 column (elution with isopropanol); tryptic peptides separated by reversed phase HPLC; amino acid analysis; S. aureus V8 protease digestion of peptide alphaXT-12B; sequencing DNA ANALYSES Not reported; presumed mutation CCC->CTC; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in three families from Northwest Africa OTHER INFORMATION Quantity in the heterozygote estimated at ~25%; high hydrophobicity of the alphaX chain REFERENCES 1. Wajcman, H., Delaunay, J., Francina, A., Rosa, J., and Galacteros, F.: Biochim. Biophys. Acta, 998:25, 1989. Hb Melusine alpha114(GH2)Pro->Ser CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation except by IEF; Hb X moves slightly slower than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES The alphaA and alphaX chain separates by reversed phase HPLC; the tryptic peptides of the AE-alphaX chain were separated by HPLC methodology; the alphaT-12B peptide was digested with S. aureus V8 protease; HPLC methodology; amino acid analysis; electro-spray mass spectrometry DNA ANALYSES Not reported; presumed mutation CCC->TCC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in an Algerian male OTHER INFORMATION The alphaX chain has a high hydrophobicity; quantity in the heterozygote is unknown REFERENCES 1. Wajcman, H., Kalmes, G., Groff, P., Prome, D., Riou, J., and Galacteros, F.: Hemoglobin, 17:397, 1993. Hb J-Tongariki alpha115(GH3)Ala->Asp CONTACT External HEMATOLOGY Microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Fingerprinting; amino acid analysis; sequencing DNA ANALYSES A GCC->GAC mutation at codon 115 occurs in the alpha2alpha1 hybrid gene of an alpha-thal-2 (3.7 kb) deletion FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in Melanesians from Tongariki Island and in the Kilengi tribe on New Guinea and Kar Kar Island OTHER INFORMATION Quantity in heterozygotes 45-50%; homozygotes 96-97% (remainder alpha2Jdelta2) REFERENCES 1. Gajdusek, D.C., Guiart, J., Kirk, R.L., Carrell, R.W., Irvine, D.L., Kynoch, P.A.M., and Lehmann, H.: N.Z. Med. J. Suppl., 65:849, 1966. 2. Abramson, R.K., Rucknagel, D.L., Shreffler, D.C., and Saave, J.J.: Science, 169: 194, 1970. 3. Old, J.M., Clegg, J.B., Weatherall, D.J., and Booth, P.B.: Nature, 273:319, 1978. Hb O-Indonesia alpha116(GH4)Glu->Lys ALSO KNOWN AS Buginese-X; Oliviere CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly slower than Hb S at alkaline pH; Hb X moves as a sharp band close to but between Hb A and Hb S on citrate agar at acidic pH; excellent separation by IEF CHROMATOGRAPHY Hb X was isolated by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES A GAG->AAG mutation at codon 116 of the alpha1 gene (Ref. 3) FUNCTIONAL STUDIES Not reported STABILITY Slightly less stable than Hb A OCCURRENCE Found in Buginese from Sulawesi (formerly Celebes), Makassars, Iranian, South African, Italian, and Chinese families OTHER INFORMATION Quantity in heterozygotes 21%; found in association with Hb D-Punjab and with beta-thal REFERENCES 1. Lie-Injo, L.E.: The Lancet, ii:1338, 1957. 2. Baglioni, C. and Lehmann, H.: Nature, 196:229, 1962. 3. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Ube-4 alpha116(GH4)Glu->Ala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly faster than Hb S at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GCG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a Japanese and a Korean family OTHER INFORMATION Quantity in heterozygotes 10-15% REFERENCES 1. Ohba, Y., Miyaji, T., Matsuoka, M., Morito, M., and Iuchi, I.: Hemoglobin, 2:181, 1978. 2. Iuchi, I., Hidaka, K., Ueda, S., Shibata, S., Hitomi, F., and Takesue, A.: Hemoglobin, 2:561, 1978. 3. Hidaka, K., Iuchi, I., Ueda, S., Shibata, S., Hitomi, F., and Takesue, A.: Kawasaki Med. J., 4:271, 1978. Hb Oleander alpha116(GH4)Glu->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves as Hb S at alkaline pH and as Hb A on citrate agar at acidic pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; glycinamidation; cation exchange chromatography; chymotrypsin; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->CAG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in a Black family OTHER INFORMATION Quantity in the heterozygote 22.3% REFERENCES 1. Schneider, R.G., Hightower, B., Carpentieri, U., Duerst, M.L., Shih, T.B., and Jones, R.T.: Hemoglobin, 6:465, 1982. Hb J-Meerut alpha120(H3)Ala->Glu ALSO KNOWN AS J-Birmingham CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A separate in cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GCG->GAG mutation has been found in codon 120 of both the alpha2 and alpha1 genes (Ref. 5) FUNCTIONAL STUDIES Not reported STABILITY Stable OCCURRENCE Found in an Indian family and in families from Japan and Turkey OTHER INFORMATION Quantity for alpha2 heterozygotes was 23%, and 19.7% for an alpha1 heterozygote (Ref. 5) REFERENCES 1. Blackwell, R.Q., Wong, H.B., Wang, C-L., Weng, M-I., and Liu, C-S.: Biochim. Biophys. Acta, 351:7, 1974. 2. Kamuzora, H., Lehmann, H., Griffiths, K.D., Mann, J.R., and Raine, D.N.: Ann. Clin. Biochem., 11:53, 1974. 3. Harano, T., Harano, K., Imai, K., Yunoki, H., Yagi, H., Nagashima, K., and Kuroume, T.: Hemoglobin, 13:169, 1989. 4. Yalcin, A., Avcu, F., Beyan, C., Gurgey, A., and Ural, A.U.: Hemoglobin, 18:433, 1994. 5. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Owari alpha121(H4)Val->Met CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X focuses between Hb A and Hb F on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Hb X was isolated by preparative IEF; alphaA and alphaX were separated by CM-cellulose chromatography; fingerprinting of the soluble peptides and of chymotryptic peptides of the soluble core; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->ATG; alpha2 or alpha1 FUNCTIONAL STUDIES Normal STABILITY Normal OCCURRENCE Found in several Japanese families OTHER INFORMATION Quantity in the heterozygote 12.7-19% REFERENCES 1. Harano, T., Harano, K., and Ueda, S.: Hemoglobin, 10:127, 1986. Hb Westmead alpha122(H5)His->Gln CONTACT alpha1beta1 contact HEMATOLOGY About normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; Hb Westmead can best be detected as an abnormal alpha chain by globin chain electrophoresis or by reversed phase HPLC CHROMATOGRAPHY Not reported STRUCTURE STUDIES Fingerprinting; amino acid analysis; chymotrypsin; Dansyl-Edman degradation DNA ANALYSES A CAC->CAG mutation at codon 122 of the alpha2 gene (Ref. 2) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in several Chinese and Laotian families OTHER INFORMATION Quantity in heterozygotes 15-20%; frequently observed in combination with alpha-thal REFERENCES 1. Fleming, P.J., Hughes, W.G., Farmilo, R.K., Wyatt, K., and Cooper, W.N.: Hemoglobin, 4:39, 1980. 2. Jiang, N.H., Liang, S., Wen, X.J., Liang, R., Su, C., and Tang, Z.: Hemoglobin, 15:291, 1991. 3. Gu, Y-C., Gu, L-H., Wilson, J.B., Cepreganova, B., Ramachandran, M., Walker, E.L.D., III, Huisman, T.H.J., and Potitong, P.: Hemoglobin, 15:297, 1991. Hb Mulhacen alpha123(H6)Ala->Ser CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS A fast-moving variant, focusing like Hb A1c CHROMATOGRAPHY No clear separation of Hb X and Hb A was observed by cation exchange HPLC STRUCTURE STUDIES Not reported; identification by sequencing of amplified DNA DNA ANALYSES A GCC->TCC mutation at codon 123 of the alpha1 gene (an additional GCG->GCT polymorphism at codon 120) FUNCTIONAL STUDIES Not reported STABILITY Stable OCCURRENCE Found in an adult Spanish male OTHER INFORMATION Quantity in the heterozygote perhaps 13-14% REFERENCES 1. Kazanetz, E.G., Leonova, J.Ye., Wilson, J.B., McMillan, S.K., Walbrecht, M., de Pablos Gallego, J.Ma., and Huisman, T.H.J.: Hemoglobin, 19:1, 1995. Hb Quong Sze alpha125(H8)Leu->Pro CONTACT Internal HEMATOLOGY Mild microcytosis, hypochromia in the heterozygote ELECTROPHORESIS Hb X cannot be detected by starch gel, cellulose acetate, or IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not possible; Hb X is detected by sequencing of amplified DNA DNA ANALYSES A CTG->CCG mutation at codon 125 of the alpha2 gene (Ref. 3) FUNCTIONAL STUDIES Not reported STABILITY Unstable; Hb X has never been observed OCCURRENCE Found in Chinese families OTHER INFORMATION Quantity in heterozygotes undetermined; observed in many Chinese families in combination with an alpha-thal-1 causing Hb H disease (alphaQSalpha/--) REFERENCES 1. Goossens, M., Lee, K.Y., Liebhaber, S.A., and Kan, Y.W.: Nature, 296:864, 1982. 2. Liebhaber, S.A. and Kan, Y.W.: J. Clin. Invest., 71:461, 1983. 3. Liang, S., Wen, X-J., and Lin, W-X.: Hemoglobin, 15:535, 1991. 4. Liang, R., Liang, S., Jiang, N.H., Wen, X-J., Zhao, J-B., Nechtman, J.F., Stoming, T.A., and Huisman, T.H.J.: Br. J. Haematol., 86:351, 1994. Hb Tarrant alpha126(H9)Asp->Asn CONTACT alpha1beta1 contact HEMATOLOGY Mild erythrocytosis in the homozygote ELECTROPHORESIS Hb X moves between Hb S and Hb F (close to Hb F) at alkaline pH and to the position of Hb S on citrate agar at acidic pH CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; chymotrypsin; amino peptidase; thermolysin DNA ANALYSES Not reported; presumed mutation GAC->AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in a few Mexican families OTHER INFORMATION Quantity in heterozygotes 20-25%; quantity in homozygotes 50% REFERENCES 1. Moo-Penn, W.F., Jue, D.L., Johnson, M.H., Wilson, S.M., Therrell, B., Jr., and Schmidt, R.M.: Biochim. Biophys. Acta, 490:443, 1977. 2. Ibarra, B., Vaca, G., Cantu, J.M., Wilson, J.B., Lam, H., Stallings, M., Gravely, M.E., and Huisman, T.H.J.: Hemoglobin, 5:337, 1981. Hb Sassari alpha126(H9)Asp->His CONTACT alpha1beta1 contact HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X moves like Hb F at pH 8.9 and like Hb C on citrate agar at pH 6.1; it moves between Hb F and Hb G-Philadelphia on IEF CHROMATOGRAPHY Hb X and Hb A separate by anion and cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; oxidation with performic acid; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->CAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a family living in Northern Sardinia OTHER INFORMATION Quantity in the heterozygote 21-24% REFERENCES 1. Masala, B., Manca, L., Stangoni, A., Cuccuru, G.B., Wilson, J.B., Webber, B.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 11:373, 1987. Hb Fukutomi alpha126(H9)Asp->Val CONTACT alpha1beta1 contact HEMATOLOGY Slight erythrocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A are best separated by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; sequence analysis DNA ANALYSES Not reported; presumed mutation GAC->GTC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; increased resistance to oxidation STABILITY Not reported OCCURRENCE Found in a 52-year-old Japanese male OTHER INFORMATION Quantity in the heterozygote 24% REFERENCES 1. Hidaka, K., Iuchi, I., Kobayashi, T., Katoh, K., and Yaguchi, K.: Hemoglobin, 14: 499, 1990. Hb Montefiore alpha126(H9)Asp->Tyr CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X migrates as Hb F at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->TAC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity and lack of cooperativity STABILITY Not reported OCCURRENCE Found in a Puerto Rican female OTHER INFORMATION Quantity in the heterozygote ~23% REFERENCES 1. Wajcman, H., Kister, J., Galacteros, F., Josifovska, O., Spielvogel, A., and Nagel, R.L.: Blood, 80:82a (Suppl. 1), 1992. Hb St. Claude alpha127(H10)Lys->Thr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; performic acid, chymotrypsin; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ACG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a family of French-Canadian descent OTHER INFORMATION Quantity in the heterozygote 27-29% REFERENCES 1. Vella, F., Galbraith, P., Wilson, J.B., Wong, S.C., Folger, G.C., and Huisman, T.H.J.: Biochim. Biophys. Acta, 365:318, 1974. Hb Jackson alpha127(H10)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J-Baltimore at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex or DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; chymotrypsin; amino acid analysis; sequen-cing; carboxypeptidase C; aminopeptidase M; chymotryptic digestion of the oxidized core DNA ANALYSES Not reported; presumed mutation AAG->AAT or AAC; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in a few Black families from the Southeastern USA OTHER INFORMATION Quantity in the heterozygote 20-25% REFERENCES 1. Moo-Penn, W.F., Bechtel, K.C., Johnson, M.H., Jue, D.L., Holland, S., Huff, C., and Schmidt, R.M.: Am. J. Clin. Pathol., 66:453, 1976. 2. Lam, H., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: J. Chromatogr., 269: 119, 1983. Hb Tunis-Bizerte alpha129(H12)Leu->Pro CONTACT Heme contact HEMATOLOGY No anemia in the heterozygote; marked anemia with microcytosis in the homozygote ELECTROPHORESIS No Hb X was detected by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES A CTG->CCG mutation at codon 129 of the alpha1 gene FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a Tunisian family; the mother is a homozygote and two children are heterozygotes OTHER INFORMATION alpha-Thalassemic phenotype REFERENCES 1. Darbellay, R., Mach-Pascual, S., Rose, K., Graf, J., and Beris, Ph.: Br. J. Haema-tol., 90:71, 1995. Hb Sun Prairie alpha130(H13)Ala->Pro CONTACT Internal HEMATOLOGY Hemolytic anemia in the proband ELECTROPHORESIS No Hb X was detectable by alkaline electrophoresis and IEF CHROMATOGRAPHY Anion and cation exchange failed to detect an abnormal Hb STRUCTURE STUDIES The globin chains were separated by reversed phase HPLC; tryptic digestion; reversed phase HPLC; amino acid analysis DNA ANALYSES A GCT->CCT mutation was observed at codon 130 of the alpha2 gene FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 4-year-old (adopted) Indian boy (homozygote), and in a 20-year-old Indian male (heterozygote) OTHER INFORMATION Quantity in the heterozygote and the homozygote ~10-11% REFERENCES 1. Harkness, M., Harkness, D.R., Kutlar, F., Kutlar, A., Wilson, J.B., Webber, B.B., Codrington, J.F., and Huisman, T.H.J.: Hemoglobin, 14:479, 1990. 2. Plaseska, D., Gu, L-H., Wilson, J.B., Codrington, J.F., Huisman, T.H.J., and Dash, S.: Hemoglobin, 14:491, 1990. Hb Yuda alpha130(H13)Ala->Asp CONTACT Internal; central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X has a pI nearly the same as Hb A1c on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES The alphaX chain was isolated by CM-cellulose chromatography; tryptic digestion; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCT->GAT; alpha2 or alpha1 FUNCTIONAL STUDIES Decreased oxygen affinity STABILITY Normal OCCURRENCE Found in a diabetic Japanese female OTHER INFORMATION The alphaX chain accounts for ~30% of total alpha REFERENCES 1. Fujisawa, K., Hattori, Y., Ohba, Y., and Ando, S.: Hemoglobin, 16:435, 1992. Hb Questembert alpha131(H14)Ser->Pro CONTACT Internal HEMATOLOGY Hemolytic anemia in the heterozygote ELECTROPHORESIS A faint abnormal band is observed by cellulose acetate at alkaline pH and by IEF CHROMATOGRAPHY Not reported; the alphaA and alphaX chains separated by reversed phase HPLC STRUCTURE STUDIES The AE-alphaX chain was digested with trypsin; the peptides were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TCT->CCT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Highly unstable OCCURRENCE Found in several members of a large French family OTHER INFORMATION Quantity in the heterozygote ~2% due to severe instability REFERENCES 1. Wajcman, H., Vasseur, C., Blouquit, Y., Rosa, J., Labie, D., Najman, A., Reman, O., Leporrier, M., and Galacteros, F.: Am. J. Hematol., 42:367, 1993. Hb Caen alpha132(H15)Val->Gly CONTACT Heme contact HEMATOLOGY Mild chronic hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X migrates between Hb F and Hb S on IEF CHROMATOGRAPHY Not reported; the alphaA and alphaX chains separate by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of AE-alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GGG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a French Caucasian woman OTHER INFORMATION Quantity in the heterozygote is low at 4-5% due to severe instability REFERENCES 1. Wajcman, H., Vasseur, C., Blouquit, Y., Rosa, J., Labie, D., Najman, A., Reman, O., Leporrier, M., and Galacteros, F.: Am. J. Hematol., 42:367, 1993. Hb Val de Marne alpha133(H16)Ser->Arg ALSO KNOWN AS Footscray CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb F and Hb A on IEF CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC STRUCTURE STUDIES The AE-alphaX chain was digested with trypsin; the peptides were separated by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGC->CGC; alpha2 or alpha1 FUNCTIONAL STUDIES Oxygen affinity moderately increased STABILITY Stable OCCURRENCE Found in four members of a French family and in a Polish-Hungarian family OTHER INFORMATION Quantity in the heterozygote estimated at 16%; asymmetric hybrid formation REFERENCES 1. Wajcman, H., Kister, J., M'Rad, A., Marden, M.C., Riou, J., and Galacteros, F.: Hemoglobin, 17:407, 1993. 2. Owen, M.C. and Hendy, J.G.: Hemoglobin, 18:19, 1994. Hb Pavie alpha135(H18)Val->Glu CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate by IEF and cellulose acetate at alkaline pH CHROMATOGRAPHY Hb X can be separated from Hb A with different types of chromatography STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GAG; alpha2 or alpha1 FUNCTIONAL STUDIES Slightly reduced oxygen affinity STABILITY Normal OCCURRENCE Found in a diabetic patient of Italian origin OTHER INFORMATION Quantity in the heterozygote ~25% REFERENCES 1. Wajcman, H., Blouquit, Y., Riou, J., Kister, J., Poyart, C., Soria, J., and Galac-teros, F.: Clin. Chim. Acta, 188:39, 1990. Hb Bibba alpha136(H19)Leu->Pro CONTACT Heme contact HEMATOLOGY Hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves like Hb S in IEF and electrophoresis at alkaline pH; freshly collected blood is required CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; chymotrypsin; sequencing DNA ANALYSES A CTG->CCG mutation at codon 136 of the alpha2 gene (Ref. 3) FUNCTIONAL STUDIES Not reported STABILITY Unstable; increased dissociation OCCURRENCE Found in a Caucasian female and several members of a Caucasian family from Alabama OTHER INFORMATION Quantity in heterozygotes most variable; clinical expression quite variable REFERENCES 1. Kleihauer, E.F., Reynolds, C.A., Dozy, A.M., Wilson, J.B., Moores, R.R., Berenson, M.P., Wright, C-S., and Huisman, T.H.J.: Biochim. Biophys. Acta, 154:220, 1968. 2. Smith, L.L., Barton, B.P., and Huisman, T.H.J.: J. Biol. Chem., 245:2185, 1970. 3. Prchal, J.T., Adler, B., Wilson, J.B., Baysal, E., Qin, W-B., Molchanova, T.P., Pobedimskaya, D.D., Kazanetz., E.G., and Huisman, T.H.J.: Hemoglobin, 19:151, 1995. Hb Toyama alpha136(H19)Leu->Arg CONTACT Heme contact HEMATOLOGY Congenital Heinz body anemia in the heterozygote ELECTROPHORESIS No abnormality was noted at alkaline pH; Hb X is so unstable that it is difficult to detect CHROMATOGRAPHY Hb X can be isolated by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Unstable OCCURRENCE Found in three members of a Japanese family OTHER INFORMATION Quantity in heterozygotes is low because of its instability REFERENCES 1. Ohba, Y., Yamamoto, K., Hattori, Y., Kawata, R., and Miyaji, T.: Hemoglobin, 11: 539, 1987. Hb Chicago alpha136(H19)Leu->Met CONTACT Heme contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Two bands, migrating slightly slower than Hb F and Hb A, were observed on IEF, but not by any other electrophoretic method CHROMATOGRAPHY No separation STRUCTURE STUDIES The alphaX, beta and alpha chains readily separate by reversed phase HPLC; tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A CTG->ATG mutation at codon 136 of the alpha2 gene (Ref. 3) FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in several Black families OTHER INFORMATION Observed in a patient with sickle cell anemia REFERENCES 1. Bowman, J.E., Bloom, R., Chen, S.S., Webber, B.B., Wilson, J.B., Kutlar, F., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 10:495, 1986. 2. Gu, L-H., Wilson, J.B., Molchanova, T.P., McKie, K.M., McKie, V.C., and Huisman, T.H.J.: Hemoglobin, 17:295, 1993. 3. Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. Hb Attleboro alpha138(H21)Ser->Pro CONTACT Internal HEMATOLOGY Mild anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate by cellulose acetate (pH 8.3); Hb X appears as a band between Hb A and Hb S CHROMATOGRAPHY Hb X and Hb A separate by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of alphaX chain; chymotryptic digestion of the insoluble core; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TCC->CCC; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a 5-year-old girl and her father OTHER INFORMATION Quantity of Hb X approximately 11% REFERENCES 1. McDonald, M.J., Michalski, L.A., Turci, S.M., Guillette, R.A., Jue, D.L., Johnson, M.H., and Moo-Penn, W.F.: Biochemistry, 29:173, 1990. Hb Tokoname alpha139(HC1)Lys->Thr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X is more anodic than Hb A by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; chymotrypsin DNA ANALYSES Not reported; presumed mutation AAA->ACA; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in a Japanese female OTHER INFORMATION Quantity in the heterozygote about 25% REFERENCES 1. Harano, T., Harano, K., Shibata, S., Ueda, S., Imai, K., and Seki, M.: Hemoglobin, 7:85, 1983. Hb Hanamaki alpha139(HC1)Lys->Glu CONTACT External HEMATOLOGY Normal-to-mild erythrocytosis in the heterozygote ELECTROPHORESIS A fast-moving band on cellulose acetate at alkaline pH and by IEF; Hb X does not separate from Hb A on agar gel CHROMATOGRAPHY Hb A and Hb X can be separated by cation exchange chromatography STRUCTURE STUDIES Tryptic digestion of alphaX chain; reversed phase HPLC to separate the soluble peptides; amino acid analysis; tandem mass spectrometry to confirm the mutation DNA ANALYSES Not reported; presumed mutation AAA->GAA; alpha2 or alpha1 FUNCTIONAL STUDIES Significantly increased oxygen affinity STABILITY Normal OCCURRENCE Found in members of a Japanese family and in a 63-year-old man, his sister, and daughter, all of English-Irish-French-Native American ancestry OTHER INFORMATION Quantity in the heterozygote about 25% REFERENCES 1. Orisaka, M., Tajima, T., Harano, T., Harano, K., Kushida, Y., and Imai, K.: Hemoglobin, 16:67, 1992. 2. Rahbar, S., Lee, T.D., Davis, M., Novotny, W.F., and Ranney, H.M.: Hemoglobin, 18:221, 1994. Hb Ethiopia alpha140(HC2)Tyr->His ALSO KNOWN AS Rouen CONTACT alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS An abnormal band can be observed by IEF close to Hb A; Hb X migrates as Hb A in cellulose acetate at alkaline pH CHROMATOGRAPHY Hb X can be separated from Hb A by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of alphaX chain; reversed phase HPLC to separate the peptides in the tryptic digest; amino acid analysis DNA ANALYSES Not reported; presumed mutation TAC->CAC; alpha2 or alpha1 FUNCTIONAL STUDIES Moderately increased oxygen affinity; decreased heme-heme interaction; Bohr effect reduced by ~40% STABILITY Normal OCCURRENCE Found in a newborn and father of Ethiopian descent; also found in an 81-year-old French male OTHER INFORMATION Quantity in the heterozygote 19-26% REFERENCES 1. Webber, B.B., Wilson, J.B., Gu, L-H., and Huisman, T.H.J.: Hemoglobin, 16:441, 1992. 2. Wajcman, H., Kister, J., Marden, M., Lahary, A., Monconduit, M., and Galacteros, F.: Biochim. Biophys. Acta, 1180:53, 1992. Hb Singapore alpha141(HC3)Arg->Pro CONTACT C-terminus HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J-Baltimore at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; chymotrypsin DNA ANALYSES Not reported; presumed mutation CGT->CCT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Normal OCCURRENCE Found in members of a family living in Singapore OTHER INFORMATION Quantity in heterozygotes about 25% REFERENCES 1. Clegg, J.B., Weatherall, D.J., Wong, H.B., and Mustafa, D.: Nature, 222:379, 1969. Hb Suresnes alpha141(HC3)Arg->His CONTACT C-terminus HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on cellulose acetate at alkaline pH; has a pI of 6.91 on IEF (Hb A 6.95) CHROMATOGRAPHY Hb X was isolated by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CGT->CAT; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity and Bohr effect STABILITY Not reported OCCURRENCE Found in a French and a Black family OTHER INFORMATION Quantity in heterozygotes 22-25% REFERENCES 1. Poyart, C., Krishnamoorthy, R., Bursaux, E., Gacon, G., and Labie, D.: FEBS Lett., 69:103, 1976. 2. Bursaux, E., Krishnamoorthy, R., Poyart, C., and Bohn, B.: INSERM, 70:277, 1977. 3. Poyart, C., Bursaux, E., Arnone, A., Bonaventura, J., and Bonaventura, C.: J. Biol. Chem., 255:9465, 1980. 4. Gravely, M.E., Harris, H.F., Stallings, M., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 2:187, 1978. Hb J-Cubujuqui alpha141(HC3)Arg->Ser CONTACT C-terminus HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on starch gel and cellulose acetate at alkaline pH; moves like Hb A on citrate agar CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase A DNA ANALYSES Not reported; presumed mutation: CGT->AGT; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity and Bohr effect STABILITY Stable OCCURRENCE Found in an Indian child living in Costa Rica and in a Mexican American OTHER INFORMATION Quantity in heterozygotes 25-29% REFERENCES 1. Saenz, G.F., Elizondo, J., Alvarado, M.A., Atmetlla, F., Arroys, G., Martinez, G., Lima, F., and Colombo, B.: Biochim. Biophys. Acta, 494:48, 1977. 2. Moo-Penn, W.F., Therrell, B.L., Jr., Jue, D.L., and Johnson, M.H.: Hemoglobin, 5:715, 1981. Hb Legnano alpha141(HC3)Arg->Leu CONTACT C-terminus HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS Hb X moves ahead of Hb A on cellulose acetate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CGT->CTT; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity; decreased cooperativity and Bohr effect STABILITY Slightly unstable OCCURRENCE Found in members of an Italian family OTHER INFORMATION Quantity in the heterozygote 32-35% REFERENCES 1. Mavilio, F., Marinucci, M., Tentori, L., Fontanarosa, P.P., Rossi, U., and Biagiotti, S.: Hemoglobin, 2:249, 1978. Hb J-Camaguey alpha141(HC3)Arg->Gly CONTACT C-terminus HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on starch gel at alkaline pH and by IEF CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digeston; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase A DNA ANALYSES Not reported; presumed mutation CGT->GGT; alpha2 or alpha1 FUNCTIONAL STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in a Cuban family of Spanish descent, a Chinese family, a family of Chinese-Australian origin, and a few Spanish families OTHER INFORMATION Quantity in the heterozygotes 18-20% REFERENCES 1. Martinez, G., Lima, F., Residenti, C., and Colombo, B.: Hemoglobin, 2:47, 1978. 2. Fei, X., Yang, K-G., Liang, C-C., Huang, Y-W., Wang, R-X., and Zhang, N-J.: Hemoglobin, 8:397, 1984. 3. Brennan, S.O., Lowrey, I.R., Harris, M.G., Rodwell, R., Zarkos, K., Wilkinson, T., Yakas, J., and Kronenberg, H.: Hemoglobin, 15:303, 1991. 4. Romero, M.J., Garrido, M.L., Abril, E., Garrido, F., and de Pablos, J.Ma.: Hemoglobin, 19:287, 1995. Hb Nunobiki alpha141(HC3)Arg->Cys CONTACT C-terminus HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS IEF showed discrete bands of Hb X, Hb A, and Hb A2, in that order CHROMATOGRAPHY Hb X and Hb A separate on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides; amino acid analysis DNA ANALYSES Not reported; presumed mutation CGT->TGT; alpha2 or alpha1 FUNCTIONAL STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a Japanese male OTHER INFORMATION Quantity in the heterozygote 13%; the cysteine residue does not participate in inter- or intra-molecular disulfide formation REFERENCES 1. Shimasaki, S.: J. Clin. Invest., 75:695, 1985. Hb Raleigh beta1(NA1)Val->Ac-Ala CONTACT 2,3-DPG binding site HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Separation of Hb X and Hb A by IEF; Hb X in position of Hb A1c (glycated Hb A) CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange chromatography (including HPLC); betaX and betaA chains can be separated by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; field desorption mass spectrometry; NMR; fingerprinting on a reversed phase column DNA ANALYSES A GTG->GCG mutation at codon 1 (Ref. 3) FUNCTION STUDIES Decreased oxygen affinity STABILITY Decreased dissociation into subunits OCCURRENCE Found in several members of a few Caucasian families; a few were also heterozygous for Hb Russ [alpha51(CE9)Gly->Arg]; also found in two Swedish families OTHER INFORMATION Quantity in the heterozygote ~45% (includes Hb A1c) REFERENCES 1. Moo-Penn, W.F., Bechtel, K.C., Schmidt, R.M., Johnson, M.H., Jue, D.L., Schmidt, D.E., Dunlap, W.M., Opella, S.J., Bonaventura, J., and Bonaventura, C.: Biochemistry, 16:4872, 1977. 2. Dubell, J.A. and Perrotta, G.: Lab. Med., 15:604, 1984. 3. Landin, B. and Jeppsson, J-O.: Hemoglobin, 17:303, 1993. Hb Deer Lodge beta2(NA2)His->Arg CONTACT 2,3-DPG binding site HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb S at alkaline pH CHROMATOGRAPHY Separation of Hb A, Hb S, and Hb X by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; cation exchange chromatography; HPLC DNA ANALYSES Not reported; presumed mutation CAC->CGC at codon 2 FUNCTION STUDIES Increased oxygen affinity, particularly below pH 6 and above pH 8; decreased cooperativity and slight increase in Bohr effect; cooperativity restored and Bohr effect reduced with the addition of 2,3-DPG and IHP STABILITY Normal OCCURRENCE Found in a few Welsh-Dutch-English and Black families; one was also heterozygous for Hb S OTHER INFORMATION Quantity in the heterozygote 40-45% REFERENCES 1. Labossiere, A., Vella, F., Hiebert, J., and Galbraith, P.: Clin. Biochem., 5:46, 1972. 2. Bonaventura, J., Bonaventura, C., Sullivan, B., and Godette, G.: J. Biol. Chem., 250: 9250, 1975. 3. Powars, D., Schroeder, W.A., Shelton, J.R., Evans, L., and Vinetz, R.: Hemoglobin, 1: 97, 1977. Hb Okayama beta2(NA2)His->Gln CONTACT 2,3-DPG binding site HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated by IEF; Hb X moves as Hb A1c CHROMATOGRAPHY Hb X was isolated by cation exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CAA or CAG at codon 2 FUNCTION STUDIES Slight increase in oxygen affinity STABILITY Normal OCCURRENCE Found in a diabetic Japanese male OTHER INFORMATION Quantity in the heterozygote 47.4% REFERENCES 1. Harano, T., Harano, K., Shibata, S., Ueda, S., Mori, H., and Arimasa, N.: FEBS Lett., 156:20, 1983. Hb Fukuoka beta2(NA2)His->Tyr CONTACT 2,3-DPG binding site HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves very close to Hb A by IEF; no abnormality was noted on cellulose acetate CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC; Hb X elutes between Hb A1c and Hb A STRUCTURE STUDIES Tryptic digestion; fingerprinting on a reversed phase HPLC column; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->TAC at codon 2 FUNCTION STUDIES Normal STABILITY Not reported OCCURRENCE Found in a Japanese female OTHER INFORMATION Quantity in the heterozygote about 40% REFERENCES 1. Harano, T., Harano, K., Ueda, S., Imai, K., Ohkuma, A., Koya, Y., and Takahashi, H.: Hemoglobin, 14:199, 1990. Hb Graz beta2(NA2)His->Leu CONTACT 2,3-DPG binding site HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X has a Hb F-like mobility on citrate agar; Hb X and Hb A can be separated by IEF CHROMATOGRAPHY Hb X and Hb A separate by cation exchange HPLC; the betaX and betaA chains can be separated by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting by reversed phase HPLC; amino acid analysis DNA ANALYSES A CAC->CTC mutation at codon 2 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Discovered in several Austrian families OTHER INFORMATION DNA analysis showed that the mutation was present in codon 2 (CAT->CTT); a polymorphim at codon 2 (CAT->CAC) was also observed; quantity in heterozygotes 41-46% REFERENCES 1. Liu, J-S., Molchanova, T.P., Gu, L-H., Wilson, J. B., Hopmeier, P., Schnedl, W., Balaun, E., Krejz, G.J., and Huisman, T.H.J.: Hemoglobin, 16:493, 1992. Hb Warwickshire beta5(A2)Pro->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS A slowly-moving variant on paper and cellulose acetate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; peptide analyses DNA ANALYSES Not reported; presumed mutation CCT->CGT at codon 5 FUNCTION STUDIES Small decrease in oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a Scottish family OTHER INFORMATION Quantity in the heterozygote 31-38% REFERENCES 1. Wilson, C.I.D., Cave, R.J., Lehmann, H., Close, M., and Imai, K.: FEBS Lett., 176:331, 1984. Hb Tyne beta5(A2)Pro->Ser CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation by any known technique, including IEF CHROMATOGRAPHY Hb X was detected by cation exchange HPLC; Hb X eluted close behind Hb A STRUCTURE STUDIES Tryptic digestion; fingerprinting on a reversed phase column; amino acid analysis DNA ANALYSES A CCT->TCT mutation at codon 5 FUNCTION STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in two unrelated English citizens OTHER INFORMATION None; quantity in the heterozygotes was not determined REFERENCES 1. Langdown, J.V., Williamson, D., Beresford, C.H., Gibb, I., Taylor, R., and Deacon-Smith, R.: Hemoglobin, 18:333, 1994. Hb S beta6(A3)Glu->Val CONTACT External HEMATOLOGY Normal in the heterozygote; hemolytic anemia of varying degrees in homozygotes; painful vasoocclusive episodes; leg ulcers; jaundice, stroke, congestive heart failure; meningitis; lowered resistance to salmonella and pneumococcus organisms ELECTROPHORESIS Hb S and Hb A can readily be separated at both alkaline and acidic pH CHROMATOGRAPHY Hb S and Hb A separate by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing; HPLC DNA ANALYSES A GAG->GTG mutation at codon 6 FUNCTION STUDIES Normal STABILITY Normal; in the deoxy form Hb S precipitates, particularly at higher salt concentrations OCCURRENCE Heterozygotes and homozygotes found in many ethnic groups but predominantly in the Black race and in some Indian tribes OTHER INFORMATION Hb S is the most studied Hb variant; relevant information can be found in all hematological text books and in many monographs; some are listed below REFERENCES 1. Bunn, H.F. and Forget, B.G.: Hemoglobin: Molecular, Genetic and Clinical Aspects, W.B. Saunders Company, Philadelphia, 1986. 2. Huisman, T.H.J., editor: The Hemoglobinopathies, Methods in Hematology, Vol. 15, Churchill Livingstone, Edinburgh, 1986. 3. Weatherall, D.J. and Higgs, D.R., editors: The Haemoglobinopathies, Bailliere's Clinical Haematology, Vol. 6, W.B. Saunders Company, London, 1993. 4. Embury, S.H., Hebbel, R.P., Mohandas, N., and Steinberg, M.H., editors: Sickle Cell Disease, Basic Principles and Clinical Practice, Raven Press, New York, 1994. 5. Miller, D.R. and Baehner, R.L., editors: Blood Diseases of Infancy and Childhood, 7th edition, Mosby-Year Book, Inc., St. Louis, MO, 1995. Hb C beta6(A3)Glu->Lys CONTACT External HEMATOLOGY Target cells in peripheral smears; mild anemia and occasionally, intraerythrocytic crystals in RBC in homozygotes ELECTROPHORESIS Hb C and Hb A readily separate at both alkaline and acid pH; Hb X moves to the position of Hb A2 on cellulose acetate and starch gel CHROMATOGRAPHY Hb C and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; Edman degradation DNA ANALYSES A GAG->AAG mutation at codon 6 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found predominantly in Blacks but also reported in many other racial and/or ethnic groups OTHER INFORMATION Quantity in heterozygotes 25-45%; homozygosity is a mild condition but SC disease is a clinically significant hemoglobinopathy; Hb C is the second most studied Hb variant; for references see the literature quoted for Hb S [beta6(A3) Glu->Val] Hb G-Makassar beta6(A3)Glu->Ala CONTACT External HEMATOLOGY Presumed normal in the heterozygote ELECTROPHORESIS Hb X moves to position of Hb S on starch gel at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GCG at codon 6 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in an Indonesian family from Southwest Sulawesi OTHER INFORMATION Quantity in the heterozygote ~45%; no sickling reported REFERENCES 1. Blackwell, R.Q., Oemijati, S., Pribadi, W., Weng, M-I., and Liu, C-S.: Biochim. Biophys. Acta, 214:396, 1970. Hb Machida beta6(A3)Glu->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves with the mobility of Hb S by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->CAG at codon 6 FUNCTION STUDIES Normal STABILITY Not reported OCCURRENCE Found in a Japanese family OTHER INFORMATION Quantity in the heterozygote 40-43% REFERENCES 1. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., and Seki, M.: Hemoglobin, 6:531, 1982. Hb G-San Jose beta7(A4)Glu->Gly CONTACT External HEMATOLOGY Normal in heterozygotes and homozygotes ELECTROPHORESIS Hb X moves between Hb S and Hb F on starch gel and cellulose acetate at alkaline pH; Hb X moves between Hb C and Hb S on citrate agar at acid pH CHROMATOGRAPHY Hb X and Hb A can be separated by cation as well as anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC; amino acid analysis; sequence analysis DNA ANALYSES Not reported; presumed mutation GAG->GGG at codon 7 FUNCTION STUDIES Normal oxygen affinity, Bohr effect, and cooperativity STABILITY Slightly unstable OCCURRENCE Mainly in Italian families; found in combination with Hb S and beta-thal; the homozygote came from Calabria (Ref. 6) OTHER INFORMATION Quantity in heterozygotes 30-40% REFERENCES 1. Schwartz, H.C., Spaet, T.H., Zuelzer, W.W., Neel, J.V., Robinson, A.R., and Kaufman, S.F.: Blood, 12:238, 1957. 2. Hill, R.L., Swenson, R.T., and Schwartz, H.C.: J. Biol. Chem., 235:3182, 1960. 3, Hill, R.L., Swenson, R.T., and Schwartz, H.C., Blood, 19:573, 1962. 4. Musumeci, S., Schiliro, G., Pizzarelli, G., Tentori, L., Marinucci, M., Fontanarosa, P.P., and Russo, G.: Hum. Genet., 52:239, 1979. 5. Wilson, J.B., Lam, H., Williams, D., Huisman, T.H.J., Espinosa-Turcott, J., and Ruiz-Reyes, G.: Hemoglobin, 4:95, 1980. 6. Brancati, C., Caracciolo, M., Bria, M., Bisconte, M.G., and Qualtieri, A.: Hemoglobin, 13:497, 1989. Hb G-Siriraj beta7(A4)Glu->Lys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb F (Tris buffer) and between Hb A2 and Hb S (barbiturate buffer) on paper at alkaline pH; Hb X moves between Hb E and Hb S on starch gel at alkaline pH, and as Hb C on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; carboxypeptidase B used to determine the C-terminal amino acid of peptide betaT-1 DNA ANALYSES Not reported; presumed mutation GAG->AAG at codon 7 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a few Thai and Chinese families OTHER INFORMATION Quantity in heterozygotes 33-40%; the variant has been found in combination with beta-thal and in a homozygote (Ref. 3) REFERENCES 1. Tuchinda, S., Beale, D., and Lehmann, H.; Br. Med. J., 1:1583, 1965. 2. Blackwell, R.Q., Liu, C-S., and Wang, C-L.: Vox Sang., 23:433, 1972. 3. Zeng, Y. and Huang, S.; Acta Genet. Sin., 6:155, 1979. Hb Rio Grande beta8(A5)Lys->Thr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb J on cellulose acetate at alkaline pH and between Hb A and Hb F on citrate agar at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->ACG at codon 8 FUNCTION STUDIES Normal oxygen affinity, 2,3-DPG, and IHP STABILITY Normal OCCURRENCE Found in members of a Mexican-American family OTHER INFORMATION Quantity in the heterozygote 48.1% REFERENCES 1. Moo-Penn, W.F., Johnson, M.H., McGuffey, J.E., Jue, D.L., and Therrell, B.L., Jr.: Hemoglobin, 7:91, 1983. Hb J-Luhe beta8(A5)Lys->Gln CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->CAG at codon 8 FUNCTION STUDIES Not known STABILITY Not known OCCURRENCE Found in a Chinese family OTHER INFORMATION None (Chinese publication) REFERENCES 1. Cai, Y-L., Wang, H-B., Yang, X-Y., Liu, Z-H., Ao, Z-F., Gong, D-H., Ma, J-P., Wang, M-J., Ma, D-R., Xu, Y-Q., and Chen, E-H.: Chinese Hematol. J., 3:263, 1982. Hb N-Timone beta8(A5)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X has a lower pI than Hb N-Baltimore on IEF; Hb X and Hb A separate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting on a reversed phase column; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->GAG at codon 8 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Discovered in a French-Italian family OTHER INFORMATION Quantity in the heterozygote not reported REFERENCES 1. Lena-Russo, D., Orsini, A., Vovan, L., Bardakdjian-Michau, J., Lacombe, C., Blouquit, Y., Craescu, C.T., and Galacteros, F.: Hemoglobin, 13:743, 1989. Hb Porto Alegre beta9(A6)Ser->Cys CONTACT External HEMATOLOGY Normal in heterozygotes and homozygotes ELECTROPHORESIS Hb X migrates the same as Hb A on starch gel (pH 8.6); Hb X and Hb A can best be separated by IEF CHROMATOGRAPHY Hb X and Hb A can be separated by DEAE-cellulose chromatography but not by cation exchange HPLC; the betaX and betaA chains partially separate by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; cation exchange chromatography; amino acid analysis; Edman degradation DNA ANALYSES A TCT->TGT mutation at codon 9 (Refs. 4 and 5) FUNCTION STUDIES Both tetramer and disulfide polymers have oxygen affinities somewhat higher than normal Hb; slightly reduced cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE In several families from Brazil, Argentina, and the Canary Islands OTHER INFORMATION Has been observed in homozygotes (Ref. 1); in association with beta-thal (Ref. 4), with Hb Santa Ana [beta88(F4)Leu->Pro (Ref. 5)] REFERENCES 1. Tondo, C.V., Salzano, F.M., and Rucknagel, D.L.: Am. J. Hum. Genet., 15:265, 1963. 2. Bonaventura, J. and Riggs, A.: Science, 158:800, 1967. 3. Tondo, C., Bonaventura, J., Bonaventura, C., Brunori, M., Amiconi, G., and Antonini, E.: Biochim. Biophys. Acta, 342:15, 1974. 4. Malcorra-Azpiazu, J.J., Wilson, J.B., Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Hemoglobin, 17:457, 1993. 5. Goncalves, M.S., Sonati, M.F., Kimura, M., Arruda, V.R., Costa, F.F., Nechtman, J.F., and Stoming, T.A.: Hemoglobin, 18:235, 1994. Hb Ankara beta10(A7)Ala->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly faster than Hb A on paper and starch gel at alkaline pH CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; Edman degradation DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 10 FUNCTION STUDIES Not determined STABILITY Stable OCCURRENCE Found in a Turkish and a few Japanese families OTHER INFORMATION Quantity in the heterozygote 42% REFERENCES 1. Arcasoy, A., Casey, R., Lehmann, H., Cavdar, A.O., and Berki, A.: FEBS Lett., 42:121, 1974. 2. Hidaka, K., Iuchi, I., Shimasaki, S., Mizuta, W., Takatsuka, M., Mori, T., Tohdoh, A., and Matsuo, M.: Hemoglobin, 10:65, 1986. Hb Hamilton beta11(A8)Val->Ile CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation observed at acid and alkaline pH; betaX and betaA separate on PAGE CHROMATOGRAPHY No separations observed and/or reported STRUCTURE STUDIES Tryptic digestion of betaA+betaX chains; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTT->ATT at codon 11 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in an Austrian family living in Canada and in a Chinese family OTHER INFORMATION Quantity in the heterozygote ~38%; one member of the Chinese family also had Hb H disease (-alpha-4.2/--SEA) (Ref. 2) REFERENCES 1. Wong, S.C., Ali, M.A.M., Lam, H., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Am. J. Hematol., 16:47, 1984. 2. Cu, C-W., Liang, S., Liang, R., Wen, X-J., and Tang, C-N.: Hemoglobin, 16:403, 1992. Hb Windsor beta11(A8)Val->Asp CONTACT Internal HEMATOLOGY Hemolytic anemia with Heinz bodies ELECTROPHORESIS A fast-moving band was seen on cellulose acetate; best separation of Hb X and Hb A by IEF CHROMATOGRAPHY No separation observed/reported STRUCTURE STUDIES Tryptic digestion of mixture of betaA+betaX chains; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTT->GAT at codon 11 FUNCTION STUDIES Increased oxygen affinity (determined for total blood or red cells) STABILITY Unstable OCCURRENCE Found in a 9-month-old female of Anglo-Saxon descent; the variant was not present in the parents, suggesting a de novo mutation OTHER INFORMATION Quantity estimated at about 30% REFERENCES 1. Gilbert, A.T., Fleming, P.J., Sumner, D.R., Hughes, W.G., Holland, R.A.B., and Tibben, E.A.: Hemoglobin, 13:437, 1989. Hb Washtenaw beta11(A8)Val->Phe CONTACT Internal HEMATOLOGY (Nearly) normal in the heterozygote; some cyanosis seen ELECTROPHORESIS No separation observed CHROMATOGRAPHY No separation observed by ion exchange chromatography; the variant was detected because the betaA and betaX chains separated by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of betaX chain; reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTT->TTT at codon 11 FUNCTION STUDIES Decreased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in several members of a Hungarian-American family OTHER INFORMATION An association between the inheritance of this abnormal Hb and the pathogenesis of primary pulmonary hypertension is suggested; quantity in the heterozygote is estimated at about 40% REFERENCES 1. Krishnan, K., Martinez, F., Wille, R.T., Jones, R.T., Shih, D.T., Head, C., Fairbanks, V.F., and Dabich, L.: Hemoglobin 18:285, 1994. Hb J-Lens beta13(A10)Ala->Asp CONTACT External HEMATOLOGY Probably normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on cellulose acetate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; Edman degradation DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 13 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 2-year-old French child; no report of a family study OTHER INFORMATION Quantity in the heterozygote + or - 50% REFERENCES 1. Djoumessi, S., Rousseaux, J., and Dautrevaux, M.: FEBS Lett., 136:145, 1981. Hb Sogn beta14(A11)Leu->Arg CONTACT Surface crevice HEMATOLOGY Normal hematology but Heinz bodies can be seen after incubation for 2 hours with acetylphenylhydrazine ELECTROPHORESIS Hb X moves as Hb S on paper, starch gel, and agar gel at alkaline pH CHROMATOGRAPHY Separation by cation exchange HPLC (Ref. 3) STRUCTURE STUDIES Fingerprinting; amino acid analysis DNA ANALYSES A CTG->CGG mutation at codon 14 (Ref. 3) FUNCTION STUDIES Normal STABILITY Mildly unstable OCCURRENCE Hb Sogn was found in a few Norwegian and American families OTHER INFORMATION Quantity in the heterozygote 29-32%; also found in combination with alpha-thal REFERENCES 1. Monn, E., Gaffney, P.J., and Lehmann, H.: Scand. J. Haematol., 5:353, 1968. 2. Monn, E. and Bjark, P.: Scand. J. Haematol., 7:455, 1970. 3. Miller, D.R., Kazanetz, E.G., Leonova, J.Ye., Smetanina, N.S., and Huisman, T.H.J.: Hemoglobin, in press (1996) Hb Saki beta14(A11)Leu->Pro CONTACT Surface crevice HEMATOLOGY Normal in the heterozygote; Heinz bodies can be seen ELECTROPHORESIS Hb X does not separate at alkaline or acidic pH; Hb X moves with Hb A on cellulose acetate, starch gel, and citrate agar CHROMATOGRAPHY No separation reported STRUCTURE STUDIES pCMB precipitation; tryptic digestion; fingerprinting; cation exchange HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTG->CCG at codon 14 FUNCTION STUDIES Normal STABILITY Unstable OCCURRENCE Found in an African female in association with Hb S and in her son; in a 15-year-old Caucasian male heterozygous for beta-thal and in his father who has Hb A and Hb Saki OTHER INFORMATION None REFERENCES 1. Beuzard, Y., Basset, P., Braconnier, F., El Gammal, H., Martin, L., Oudard, J.L., and Thillet, J.: Biochim. Biophys. Acta, 393:182, 1975. 2. Milner, P.F., Corley, C.C., Pomeroy, W.L., Wilson, J.B., Gravely, M., and Huis-man, T.H.J.: Am. J. Hematol., 1:283, 1976. Hb Belfast beta15(A12)Trp->Arg CONTACT Internal; A-E helices spacer HEMATOLOGY Approximately normal in the heterozygote; Heinz bodies can be seen ELECTROPHORESIS Hb X moves as Hb S on cellulose acetate at alkaline pH, and like Hb A on citrate agar at acidic pH CHROMATOGRAPHY DEAE-Sephadex was used to isolate Hb X STRUCTURE STUDIES Fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGG->AGG or CGG at codon 15 FUNCTION STUDIES Increased oxygen affinity STABILITY Unstable OCCURRENCE Found in a few Irish and French patients OTHER INFORMATION Quantity in heterozygotes 27.5-29% REFERENCES 1. Kennedy, C.C., Blundell, G., Lorkin, P.A., Lang, A., and Lehmann, H.: Br. Med. J., 4:324, 1974. 2. Gacon, G., Wajcman, H., Labie, D., Varet, B., and Christoforov, G.: Acta Haematol., 55:313, 1976. Hb Randwick beta15(A12)Trp->Gly CONTACT Internal; A-E helices spacer HEMATOLOGY Normal in the heterozygote; mild reticulocytosis ELECTROPHORESIS Hb X moves faster than Hb A on cellulose acetate at alkaline pH; Hb X and Hb A can be separated by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; fingerprinting by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGG->GGG at codon 15 FUNCTION STUDIES Normal STABILITY Unstable OCCURRENCE Found in members of a Northern Italian family OTHER INFORMATION Quantity in the heterozygote estimated at 48-50% REFERENCES 1. Gilbert, A.T., Fleming, P.J., Sumner, D.R., Hughes, W.G., Ip, F., Kwan, Y.L., and Holland, R.A.B.: Hemoglobin, 12:149, 1988. Hb J-Baltimore beta16(A13)Gly->Asp ALSO KNOWN AS J-Trinidad; J-Ireland; N-New Haven; J-Georgia CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on paper and starch gel at alkaline pH; Hb X moves as Hb S on citrate agar at pH 5.9; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGC->GAC at codon 16 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in Black, English, Dutch, French, Swedish, and Spanish families; sometimes together with Hb S or with beta-thal OTHER INFORMATION Quantity in heterozygotes 40-45% REFERENCES 1. Baglioni, C. and Weatherall, D.J.: Biochim. Biophys. Acta, 87:637, 1963. 2. Wong, S.C., Bouver, N., Wilson, J.B., and Huisman, T.H.J.: Clin. Chim. Acta, 16:368, 1971. 3. Landin, B. and Jeppsson, J-O.: Hemoglobin, 17:303, 1993. 4. Arribalzaga, K., Ricard, M.P., Carreno, D.L., Sanchez, J., Gonzalez, A., Ropero, P., and Villegas, A.: Hemoglobin, 20:79, 1996. Hb D-Bushman beta16(A13)Gly->Arg CONTACT External HEMATOLOGY Probably normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on starch block at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC at codon 16 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in members of a Kalahari Bushman family OTHER INFORMATION Quantity in heterozygotes 34-39% REFERENCES 1. Wade, P.T., Jenkins, T., and Huehns, E.R.: Nature, 216:688, 1967. Hb Nagasaki beta17(A14)Lys->Glu CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb X moves faster than Hb A on starch gel at alkaline pH CHROMATOGRAPHY Hb X was isolated by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->GAG at codon 17 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in three members of a Japanese family living in Nagasaki, Japan OTHER INFORMATION Quantity in the heterozygote 30%; heterozygotes appear to be clinically normal REFERENCES 1. Maekawa, M., Maekawa, T., Fujiwara, N., Tabara, K., and Matsuda, G.: Int. J. Prot. Res., II:147, 1970. Hb J-Amiens beta17(A14)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb J on cellulose acetate at alkaline pH; Hb X moves with Hb A on citrate agar at pH 6.2; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT at codon 17 FUNCTION STUDIES Normal oxygen affinity, cooperativity, and 2,3-DPG level STABILITY Normal OCCURRENCE Found in a Spanish female and in a Japanese male OTHER INFORMATION Quantity in the heterozygote 40-45% REFERENCES 1. Elion, J., Wajcman, H., Belkhodja-Dunda, O., Lapoumeroulie, C., Labie, D., Messerschmitt, J., Staal, A.M., and Desablens, B.: Nouv. Rev. Fr. d'Hematol., 21:347, 1979. 2. Harano, T., Harano, K., Kushida, Y., Ueda, S., Kawakami, H.: Hemoglobin, 14: 445, 1990. Hb Nikosia beta17(A14)Lys->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate on cellulose acetate at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->CAG at codon 17 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Cypriot living in Russia OTHER INFORMATION None REFERENCES 1. Spivak, V.A.: Hemoglobin, 13:219, 1989. Hb Baden beta18(A15)Val->Met CONTACT Internal HEMATOLOGY Unknown; the mutation resulting in this variant occurred on a chromosome with the beta+-thal mutation IVS-I-5 (G->C) ELECTROPHORESIS Not observed CHROMATOGRAPHY Hb X and Hb A separate incompletely by cation exchange HPLC; the betaX and betaA chains do not separate in reversed phase HPLC STRUCTURE STUDIES Not done; structural analyses by DNA sequencing DNA ANALYSES A GTG->ATG mutation at codon 18 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a mother and son from East Germany OTHER INFORMATION None REFERENCES 1. Divoky, V., Bisse, E., Wilson, J.B., Gu, L-H., Wieland, H., Heinrichs, I., Prior, J.F., and Huisman, T.H.J.: Biochim. Biophys. Acta, 1180:173, 1992 . Hb Sinai-Baltimore beta18(A15)Val->Gly CONTACT Internal HEMATOLOGY Mild anemia with marked microcytosis and hypochromia, likely because of an additional alpha-thal ELECTROPHORESIS Hb X was detected by IEF; it moved just behind Hb A CHROMATOGRAPHY Hb X and Hb A separate incompletely by cation exchange HPLC; reversed phase HPLC separated betaX from betaA and betaS STRUCTURE STUDIES Tryptic digestion; reversed phase HPLC; amino acid analysis DNA ANALYSES A GTG->GGG mutation at codon 18 FUNCTION STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in a Black family OTHER INFORMATION Quantity in the heterozygote 35-40%; the variant has been observed in combination with Hb S REFERENCES 1. Pobedimskaya, D.D., Molchanova, T.P., Amernick, R., Druskin, M.S., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 17:505, 1993. Hb D-Ouled Rabah beta19(B1)Asn->Lys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S on paper at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->AAA or AAG at codon 19 FUNCTION STUDIES Not done STABILITY Not done OCCURRENCE Found in an Algerian family and in 60 members of a Tuareg tribe of the Southern Sahara OTHER INFORMATION Quantity in heterozygotes 40-47% REFERENCES 1. Elion, J., Belkhodja, O., Wajcman, H., and Labie, D.: Biochim. Biophys. Acta, 310:360, 1973. 2. Braconnier, F., Beuzard, Y., El Gammal, H., Coquelet, M.T., and Rosa, J.: Nouv. Rev. Fr. d'Hematol., 15:527, 1975. 3. Mauran-Sendrail, A., Lefevre-Witier, Ph., Lehmann, H., and Casey, R.: Br. Med. Genet., 14:245, 1977. Hb Alamo beta19(B1)Asn->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A on starch gel at alkaline pH, and to the position of Hb A on citrate agar at acidic pH CHROMATOGRAPHY Hb X and Hb A were separated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->GAC at codon 19 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Black family OTHER INFORMATION Quantity in the heterozygote 52-54% (some Hb A1 is probably included) REFERENCES 1. Lam, H., Wilson, J.B., Harris, H., Gravely, M., and Huisman, T.H.J.: Hemoglobin, 1:703, 1977. Hb Malay beta19(B1)Asn->Ser CONTACT External HEMATOLOGY Mild microcytosis and hypochromia in the heterozygote, which are more severe in the homozygote ELECTROPHORESIS No separation reported CHROMATOGRAPHY No separation of Hb X and Hb A by cation exchange HPLC; betaX and betaA can be separated by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES An AAC->AGC mutation at codon 19 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Discovered in Malay patients; as heterozygotes, homozygotes, and in combination with Hb E OTHER INFORMATION The AAC->AGC mutation at codon 19 creates an alternative splicing site between codons 17 and 18, reducing the efficiency of the normal donor site at IVS-I to about 60%; this makes Hb Malay a "thalassemic" Hb type REFERENCES 1. Yang, K.G., Kutlar, F., George, E., Wilson, J.B., Kutlar, A., Stoming, T.A., Gonzalez-Redondo, J.M., and Huisman, T.H.J.: Br. J. Haematol., 72:73, 1989. Hb Olympia beta20(B2)Val->Met CONTACT External HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation obtained CHROMATOGRAPHY No separation obtained STRUCTURE STUDIES Tryptic digestion of the betaA and betaX chain; fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GTG->ATG mutation at codon 20 (unpublished data) FUNCTION STUDIES Increased oxygen affinity; cooperativity, 2,3-DPG, and Bohr effects appear normal STABILITY Slightly unstable OCCURRENCE Found in a few Caucasian families OTHER INFORMATION None REFERENCES 1. Stamatoyannopoulos, G., Nute, P.E., Adamson, J.W., Bellingham, A.J., and Funk, D.: J. Clin. Invest., 52:342, 1973. 2. Nakatsuji, T., Wilson, J.B., Lam, H., and Huisman, T.H.J.: J. Chromatogr., 259: 511, 1983. 3. Berlin, G. and Wranne, B.: Hemoglobin, 13:493, 1989. Hb Trollhattan beta20(B2)Val->Glu CONTACT External HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A separate by anion exchange HPLC STRUCTURE STUDIES Lysylendopeptidase digestion; reversed phase HPLC; amino acid analysis DNA ANALYSES A GTG->GAG mutation at codon 20 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a Swedish family OTHER INFORMATION Quantity in the heterozygote 48-51%; mutation was confirmed by restriction enzyme analysis (Mae II) REFERENCES 1. Landin, B., Berglund, S., and Lindoff, B.: Eur. J. Haematol., 53:21, 1994. Hb Yusa beta21(B3)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A separate on an anion exchange column STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC: amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->TAT at codon 21 FUNCTION STUDIES Normal oxygen affinity, Bohr, cooperativity, and 2,3-DPG effects STABILITY Normal OCCURRENCE Found in two Japanese families OTHER INFORMATION Quantity in heterozygotes ~41% REFERENCES 1. Harano, T., Harano, K., Ueda, S., Shibata, S., and Iuchi, I.: Hemoglobin, 5:121, 1981. 2. Ohba, Y., Hattori, Y., Ami, M., Yagami, H., Miyaji, T., and Tani, Y.: Hemoglobin, 14:109, 1990. Hb Connecticut beta21(B3)Asp->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb S CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->GGT at codon 21 FUNCTION STUDIES Decreased oxygen affinity; normal cooperativity and Bohr effect; slight decrease in the effect of allosteric effectors on the oxygen equilibrium properties of the variant STABILITY Normal OCCURRENCE Found in members of a family of Polish origin living in the United States OTHER INFORMATION Quantity in the heterozygote 39-43% REFERENCES 1. Moo-Penn, W.F., McPhedran, P., Bobrow, S., Johnson, M.H., Jue, D.L., and Olsen, K.W.: Am. J. Hematol., 11:137, 1981. Hb Cocody beta21(B3)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves like Hb S); excellent separation on IEF CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC; the betaA and betaX chains separate completely by reversed phase HPLC STRUCTURE STUDIES Proteolytic digestion; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 21 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a family from the Ivory Coast and in a Japanese family OTHER INFORMATION Quantity in the heterozygote ~44% REFERENCES 1. Boissel, J.P., Wajcman, H., Fabritius, H., Cabannes, R., and Labie, D.: Biochim. Biophys. Acta, 670:203, 1981. 2. Ohba, Y., Hattori, Y., Ami, M., Yagami, H., Miyaji, T., and Tani, Y.: Hemoglobin, 14:109, 1990. Hb Karlskoga beta21(B3)Asp->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC STRUCTURE STUDIES Proteolytic digestion; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAT->CAT mutation at codon 21 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Swedish woman OTHER INFORMATION Quantity in the heterozygote 39% REFERENCES 1. Landin, B.: Hemoglobin, 17:201, 1993. Hb E-Saskatoon beta22(B4)Glu->Lys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves about as Hb A2 CHROMATOGRAPHY Hb X and Hb A separate in cation and anion exchange chromatography; Hb E-Saskatoon and Hb E can be separated by cation exchange HPLC; both elute behind Hb A at slightly different positions in the chromatogram STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAA->AAA at codon 22 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in several families of Scottish descent; the variant might have originated in the Orkney Islands, Scotland; also found in some Turkish families, and in a Japanese male OTHER INFORMATION Quantity in the heterozygote 35-40%; has been observed in combination with beta-thal REFERENCES 1. Vella, F., Lorkin, P.A., Carrell, R.W., and Lehmann, H.; Can. J. Biochem., 45: 1384, 1967. 2. Tills, D., Muir, V., Warlow, A., Hopkinson, D.A., Lorkin, P.A., El-Hazmi, M.A.F., and Lehmann, H.: Hum. Genet., 33:179, 1976. 3. Gurgey, A., Sipahioglu, M., and Aksoy, M.: Hemoglobin, 14:449, 1990. 4. Igarashi, Y., Matsuzaki, S., Kanou, N., Inami, S., Nakamura, T., Kasai, K., and Fushitani, K.: Hemoglobin, 19:403, 1995. Hb G-Taipei beta22(B4)Glu->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves about as Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by cation exchange HPLC; the betaA and betaX chains separate completely by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAA->GGA at codon 22 FUNCTION STUDIES Not reported STABILITY Stable OCCURRENCE Found in a few Chinese families OTHER INFORMATION Quantity in the heterozygote 36-40% REFERENCES 1. Blackwell, R.Q., Yang, H.J., and Wang, C.C.: Biochim. Biophys. Acta, 174: 237, 1969. 2. Landman, H., Wilson, J.B., Kutlar, A., Gonzalez Redondo, J.M., and Huisman, T.H.J.: Hemoglobin, 11:169, 1987. Hb G-Coushatta beta22(B4)Glu->Ala ALSO KNOWN AS G-Saskatoon; G-Hsin Chu; G-Taegu CONTACT External HEMATOLOGY Normal in the heterozygote and homozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves about as Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAA->GCA at codon 22 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Observed in Indians, Chinese, Koreans, Japanese, Turks, Algerians, etc. OTHER INFORMATION Quantity in the heterozygote 38-45%; a homozygote has been detected; also observed in combination with beta-thal REFERENCES 1. Vella, F., Isaacs, W.A., and Lehmann, H.: Can. J. Biochem., 45:351, 1967. 2. Blackwell, R.Q., Ro, I-H., Liu, C-S., Yang, H-J., Wang, C-C., and Huang, J.T-H.: Am. J. Phys. Anthropol., 30:389, 1969. 3. Dincol, G., Dincol, K., and Erdem, S.: Hemoglobin, 13:75-1989. Hb D-Iran beta22(B4)Glu->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A readily separate at alkaline pH; excellent separation by IEF; Hb X moves about as Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange HPLC STRUCTURE STUDIES Proteolytic digests; fingerprinting; reversed phase HPLC; amino acid analysis; sequencing by Edman degradation DNA ANALYSES Not reported; presumed mutation GAA->CAA at codon 22 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in Iranian and Pakistani families; a Jamaican Black, and several families in Northern Calabria, Italy OTHER INFORMATION Quantity in the heterozygote 36-45%; observed in combination with Hb S and with beta-thal REFERENCES 1. Rahbar, S.: Br. J. Haematol., 24:31, 1973. 2. Rohe, R.A., Sharma, V., and Ranney, H.M.: Blood, 42:455, 1973. 3. De Marco, E.V., Crescibene, L., Bagala, A., Brancati, C., Qualtieri, A., and Bria, M.: Hemoglobin, 18:65, 1994. Hb D-Granada beta22(B4)Glu->Val CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves about as Hb S CHROMATOGRAPHY Hb X and Hb A separate in cation and in anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides on a reversed phase HPLC column; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAA->GTA at codon 22 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Gypsy family in Granada, Spain OTHER INFORMATION Quantity in the heterozygote 42.6% REFERENCES 1. de Pablos, J.Ma., Kutlar, A., Wilson, J.B., Webber, B.B., Hu, H., and Huisman, T.H.J.: Hemoglobin, 11:563, 1987. Hb Strasbourg beta23(B5)Val->Asp CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate completely by IEF; Hb X focuses ahead of Hb A CHROMATOGRAPHY Hb X and Hb A could not be separated by routine chromatographic methods STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing by Edman degradation and Dansylation DNA ANALYSES Not reported; presumed mutation GTT->GAT at codon 23 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect; decreased cooperativity STABILITY Normal OCCURRENCE Found in a Portuguese female from Northern Portugal OTHER INFORMATION Quantity in the heterozygote ~40% REFERENCES 1. Garel, M.C., Blouquit, Y., Arous, N., and Rosa, J.: FEBS Lett., 72:1, 1976. 2. Forget, B.G., Hemoglobin, 1:879, 1977. 3. Cohen-Solal, M., North, M.L., Thillet, J., Albrecht-Ellmer, K., Garel, M.C., Blouquit, Y., and Rosa, J.: FEBS Lett., 90:286, 1978. Hb Miyashiro beta23(B5)Val->Gly CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A cannot be separated with routine electrophoretic procedures CHROMATOGRAPHY No detailed information available STRUCTURE STUDIES Fingerprinting; amino acid analysis; Dansyl-Edman degradation DNA ANALYSES Not reported; presumed mutation GTT->GGT at codon 23 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect; decreased cooperativity STABILITY Unstable OCCURRENCE Found in members of a Japanese family OTHER INFORMATION Quantity in the heterozygote estimated at 29-38% REFERENCES 1. Nakatsuji, T., Miwa, S., Ohba, Y., Hattori, Y., Miyaji, T., Miyata, H., Shinohara, T., Hori, T., and Takayama, J.: Hemoglobin, 5:653, 1981. Hb Palmerston North beta23(B5)Val->Phe CONTACT Internal HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; Hb X moves approximately like Hb F in IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; reversed phase HPLC; amino acid analysis; Dansyl-Edman degradation DNA ANALYSES Not reported; presumed mutation GTT->TTT at codon 23 FUNCTION STUDIES Increased oxygen affinity; normal cooperativity STABILITY Slightly unstable OCCURRENCE Found in a 73-year-old female in New Zealand OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Brennan, S.O., Williamson, D., Whisson, M.E., and Carrell, R.W.: Hemoglobin, 6:569, 1982. Hb Riverdale-Bronx beta24(B6)Gly->Arg CONTACT Internal; close contact with the E helix HEMATOLOGY Mild hemolytic anemia with reticulocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X takes the position of Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGT->CGT at codon 24 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect, and cooperativity STABILITY Unstable OCCURRENCE Found in a female of German-Jewish ancestry OTHER INFORMATION Quantity in the heterozygote 30%; splenomegaly present REFERENCES 1. Ranney, H.M., Jacobs, A.S., Uden, L., and Zalusky, R.: Biochem. Biophys. Res. Commun., 33:1004, 1968. 2. Bank, A., O'Donnell, J.V., and Braverman, A.S.: J. Lab. Clin. Med., 76:616, 1970. 3. Farace, M.G. and Bank, A.: Biochim. Biophys. Acta, 312:591, 1973. Hb Savannah beta24(B6)Gly->Val CONTACT Internal; close contact with the E helix HEMATOLOGY Hemolytic anemia with reticulocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A do not separate well at alkaline pH; some of the variant Hb moves to the position of Hb S CHROMATOGRAPHY No good separation reported by either cation or anion exchange chromatography STRUCTURE STUDIES pCMB precipitation; tryptic digestion; cation exchange chromatography; thermolysin digestion; sequencing DNA ANALYSES Not reported; presumed mutation GGT->GTT at codon 24 FUNCTION STUDIES Not reported STABILITY Unstable; increased dissociation into dimers and monomers OCCURRENCE Found in an 8-year-old Caucasian child but not in her parents or her seven siblings OTHER INFORMATION Quantity in the heterozygote estimated at ~30%; splenectomy at 19 months of age REFERENCES 1. Huisman, T.H.J., Brown, A.K., Efremov, G.D., Wilson, J.B., Reynolds, C.A., Uy, R., and Smith, L.L.: J. Clin. Invest., 50:650, 1971. Hb Moscva beta24(B6)Gly->Asp CONTACT Internal; close contact with the E helix HEMATOLOGY Hemolytic anemia with reticulocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; thermolysin digestion; sequencing DNA ANALYSES Not reported; presumed mutation GGT->GAT at codon 24 FUNCTION STUDIES Slightly decreased oxygen affinity; small change in Bohr effect and cooperativity STABILITY Unstable OCCURRENCE Found in a few members of a Russian family OTHER INFORMATION Quantity in the heterozygote not determined REFERENCES 1. Idelson, L.I., Didkowsky, N.A., Casey, R., Lorkin, P.A., and Lehmann, H.: Nature, 249:768, 1974. Hb G-Taiwan-Ami beta25(B7)Gly->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate well at alkaline pH; Hb X takes the position of Hb G or Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; C-terminal analysis by carboxypeptidase A and B; sequencing DNA ANALYSES Not reported; presumed mutation GGT->CGT at codon 25 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in several Aborigines of the Ami tribe in Taiwan OTHER INFORMATION None REFERENCES 1. Blackwell, R.Q. and Liu, C-S.: Biochem. Biophys. Res. Commun., 30:690, 1968. Hb J-Auckland beta25(B7)Gly->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate well at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGT->GAT at codon 25 FUNCTION STUDIES Decreased oxygen affinity STABILITY Mildly unstable OCCURRENCE Found in a family of Scandinavian and Scottish descent OTHER INFORMATION Quantity in heterozygotes 40-50% REFERENCES 1. Williamson, D., Wells, R.M.G., Anderson, R., and Matthews, J.: Hemoglobin, 11: 221, 1987. Hb E beta26(B8)Glu->Lys CONTACT External HEMATOLOGY Mild microcytosis in heterozygotes; normal to mild anemia, reduced red cell survival, reduced MCV, target cells, reduced osmotic fragility in homozygotes ELECTROPHORESIS Hb E and Hb A can readily be separated at alkaline pH but not at acidic pH; Hb E moves much slower than Hb A, just ahead of Hb A2 and Hb C CHROMATOGRAPHY Hb E and Hb A separate at cation and anion exchange chromatography; it elutes with Hb A2 in several chromatographic systems, including cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES A GAG->AAG mutation at codon 26 FUNCTION STUDIES Purified Hb E has a normal oxygen affinity STABILITY Mildly unstable; it is sensitive to oxidative stress OCCURRENCE Widespread in the Far East; has been observed in combination with various Hb variants, including Hb S, Hb C, Hb D, Hb I, etc., and with different beta-thal alleles OTHER INFORMATION Quantity in the heterozygote with four alpha genes (alphaalpha/alphaalpha) ~30%; Hb E is one of the most frequently studied variants; references can be found in the listed monographs REFERENCES 1. Weatherall, D.J. and Higgs, D.R., editors: The Haemoglobinopathies, Bailliere's Clinical Haematology, Vol. 6, W.B. Saunders Company, London, 1993. 2. Miller, D.R. and Baehner, R.L., editors: Blood Diseases of Infancy and Childhood, 7th edition, Mosby-Year Book, Inc., St. Louis, MO, 1995. Hb Henri Mondor beta26(B8)Glu->Val CONTACT External HEMATOLOGY Mild hypochromic microcytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A2 can be separated at alkaline pH; Hb X moves between Hb F and Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GTG at codon 26 FUNCTION STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in a 9-year-old African female OTHER INFORMATION Quantity in the heterozygote 37.5% REFERENCES 1. Blouquit, Y., Arous, N., Machado, P.E.A., and Garel, M.C.: FEBS Lett., 72:5, 1976. Hb Volga beta27(B9)Ala->Asp ALSO KNOWN AS Drenthe CONTACT Internal HEMATOLOGY Chronic hemolytic anemia with Heinz bodies, anisocytosis, polycythemia, and basophilic stippling ELECTROPHORESIS Hb X and Hb A do not separate at alkaline or acidic pH; zone free alpha chains observed CHROMATOGRAPHY Not reported STRUCTURE STUDIES pCMB isolation; tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; thermolysin digestion; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 27 FUNCTION STUDIES Not performed STABILITY Unstable OCCURRENCE Found in a 16-year-old Russian male but not in his parents or sister; six members of a Dutch family, and in a 4-year-old Egyptian male OTHER INFORMATION Quantity in the heterozygote ~30% (based on heat denaturation data); splenectomy appears to be beneficial REFERENCES 1. Idelson, L.I., Didkowsky, N.A., Filippova, A.V., Casey, R., Kynoch, P.A.M., and Lehmann, H.: FEBS Lett., 58:122, 1975. 2. Kuis-Reerink, J.D., Jonxis, J.H.P., Niazi, G.A., Wilson, J.B., Bolch, K.C., Gravely, M., and Huisman, T.H.J.: Biochim. Biophys. Acta, 439:63, 1976. 3. Brennan, S.O., Ekert, H., Tauro, G., and Carrell, R.W.: N.Z. Med. J., 83:162, 1976. Hb Knossos beta27(B9)Ala->Ser CONTACT Internal HEMATOLOGY Heterozygote: Normal values but with mild microcytosis and hypochromia; homozygote: Moderate anemia with severe microcytosis and hypochromia ELECTROPHORESIS No separation at alkaline and acidic pH; Hb X and Hb A can be separated by IEF; more cathodal but very close to Hb A CHROMATOGRAPHY Hb X and Hb A do not separate by cation exchange chromatography; the betaX and betaA chains can be separated by reversed phase HPLC in which betaX elutes ahead of betaA, and also by PAGE STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GCC->TCC mutation at codon 27 FUNCTION STUDIES Decreased oxygen affinity STABILITY Normal OCCURRENCE Found in various Mediterranean families; also in combination with classical beta-thal, and with Hb S OTHER INFORMATION Quantity in the heterozygote 35-40%; thalassemic features due to the creation of an alternate splicing site REFERENCES 1. Fessas, Ph., Loukopoulos, D., Loutradi-Anagnostou, A., and Komis, G.: Br. J. Haema-tol., 51:577, 1982. 2. Arous, N., Galacteros, F., Fessas, Ph., Loukopoulos, D., Blouquit, Y., Komis, G., Sellaye, M., Boussiou, M., and Rosa, J.: FEBS Lett., 147:247, 1982. 3. Fessas, Ph., Loukopoulos, D., Kokkinou, S., Papasotiriou, Y., and Karaklis, A.: Am. J. Hematol., 21:119, 1986. 4. Baklouti, F., Dorleac, Morle, L., Laselve, P., Peyramond, D., Aubry, M., Godet, J., and Delaunay, J.: Blood, 67:957, 1986. 5. Kutlar, A., Kutlar, F., Aksoy, M., Gurgey, A., Altay, C., Wilson, J.B., Diaz-Chico, J.C., and Huisman, T.H.J.: Hemoglobin, 13:7, 1989. Hb Grange-Blanche beta27(B9)Ala->Val CONTACT Internal HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS No separation at alkaline or acidic pH; separation by IEF is possible; Hb X migrates slightly more cathodic than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaA+betaX chains; separation of peptides on reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->GTC at codon 27 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a Portuguese mother and daughter OTHER INFORMATION Quantity in the heterozygote ~50% (IEF data) REFERENCES 1. Baklouti, F., Giraud, Y., Francina, A., Richard, G., Perier, C., Geyssant, A., Jaubert, J., Brizard, C., and Delaunay, J.: FEBS Lett., 223:59, 1987. Hb Saint Louis beta28(B10)Leu->Gln CONTACT Internal HEMATOLOGY Chronic hemolytic anemia associated with cyanosis, methemoglobinemia, and Heinz body formation ELECTROPHORESIS A slowly-moving component can be observed at alkaline pH and by IEF; pattern changes considerably upon addition of KCN CHROMATOGRAPHY No clear separation when KCN is added to the sample; the betaX and betaA chains separate well by reversed phase HPLC STRUCTURE STUDIES The betaX chain was isolated by pCMB or by reversed phase HPLC; tryptic digestion; fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTG->CAG at codon 28 FUNCTION STUDIES Increased oxygen affinity; reduced cooperativity; normal Bohr effect; interaction with 2,3-DPG decreased STABILITY Unstable OCCURRENCE Found in a 20-year-old French male but not in his parents or siblings, and in a Yugoslavian-Slovakian teenager OTHER INFORMATION Quantity in the heterozygote 30%; splenectomy improves the clinical and hematological condition; spontaneous metHb formation; hemichrome present REFERENCES 1. Cohen-Solal, M., Seligmann, M., Thillet, J., and Rosa, J.: FEBS Lett., 33:37, 1973. 2. Thillet, J., Cohen-Solal, M., Seligmann, M., and Rosa, J.: J. Clin. Invest., 58:1098, 1976. 3. Wiedermann, B.F., Indrak, K., Wilson, J.B., Webber, B.B., Yang, K.G., Kutlar, F., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 10:673, 1986. Hb Genova beta28(B10)Leu->Pro ALSO KNOWN AS Hyogo CONTACT Internal HEMATOLOGY Congenital hemolytic anemia associated with Heinz bodies ELECTROPHORESIS No separation from Hb A CHROMATOGRAPHY No separation from Hb A; the betaX and betaA chains can be separated by reversed phase HPLC STRUCTURE STUDIES Isolation of the betaX chain by pCMB; tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CCG at codon 28 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity STABILITY Unstable OCCURRENCE Found in a few families from Europe, East India, Kenya, Cuba, Libya, and Japan OTHER INFORMATION Quantity in the heterozygote not accurately determined REFERENCES 1. Sansone, G., Carrell, R.W., and Lehmann, H.: Nature, 214:877, 1967. 2. Cohen-Solal, M. and Labie, D.: Biochim. Biophys. Acta, 295:67, 1973. 3. Hopmeier, P., Binder, C., Gadner, H., and Fischer, M.: Acta Haematol., 83:39, 1990. Hb Chesterfield beta28(B10)Leu->Arg CONTACT Internal HEMATOLOGY Severe heterozygous beta-thal ELECTROPHORESIS No abnormal Hb could be detected on electrophoresis at pH 8.6 but separation of in vitro labeled globin chains showed a betaX peak eluting after the normal betaA chain CHROMATOGRAPHY No separation reported (see above) STRUCTURE STUDIES None reported DNA ANALYSES A CTG->CGG mutation at codon 28 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 34-year-old English woman OTHER INFORMATION The mutation at codon 28 abolishes a Bst NI restriction site that will aid in the identification REFERENCES 1. Thein, S.L., Best, S., Sharpe, J., Paul, B., Clark, D.J., and Brown, M.J.: Blood, 77:2791, 1991. Hb Lufkin beta29(B11)Gly->Asp CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS This fast-moving variant readily separates from Hb A at alkaline pH and by IEF CHROMATOGRAPHY Partial separation of Hb X and Hb A by cation exchange HPLC; the betaX and betaA chains also separate incompletely by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES A GGC->GAC mutation at codon 29 (Ref. 2) FUNCTION STUDIES Increased oxygen affinity at acid pH; normal Bohr effect; normal cooperativity at physiological pH STABILITY Mildly unstable OCCURRENCE Found in two Black families; in one subject it occurred together with Hb S OTHER INFORMATION Quantity of Hb X in the subject with Hb S-Hb Lufkin disease was 46% REFERENCES 1. Schmidt, R.M., Bechtel, K.C., Johnson, M.H., Therrell, B.L., Jr., and Moo-Penn, W.F.: Hemoglobin, 1:799, 1977. 2. Gu, L-H., Leonova, J.Ye., and Huisman, T.H.J.: Hemoglobin, 19:291, 1995. Hb Tacoma beta30(B12)Arg->Ser CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote; Heinz bodies ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is slightly faster than Hb A; best separation is obtained by IEF CHROMATOGRAPHY Separation of Hb X and Hb A by anion exchange chromatography and by cation exchange HPLC STRUCTURE STUDIES Proteolytic digestion of betaX+betaA chains; reversed phase HPLC or cation exchange chromatography; amino acid analysis DNA ANALYSES An AGG->AGT mutation at codon 30 (Ref. 3); codon 30 is divided by intron 1 as follows: ---CTT*AGG*CTG*CTG---. It is the first nt G of exon 2 that is changed to T FUNCTION STUDIES Normal oxygen affinity; decreased Bohr effect and cooperativity STABILITY Unstable OCCURRENCE Found in a few North European families (Russia, Finland, Sweden, USA) OTHER INFORMATION Quantity in heterozygotes 43% REFERENCES 1. Baur, E.W. and Motulsky, A.G.: Humangenetik, 1:621, 1965. 2. Brimhall, B., Jones, R.T., Baur, E.W., and Motulsky, A.G.: Biochemistry, 8:2125, 1969. 3. Landin, B. and Jeppsson, J-O.: Hemoglobin, 17:303, 1993. Hb Monroe beta30(B12)Arg->Thr ALSO KNOWN AS Kairouan CONTACT alpha1beta1 contact HEMATOLOGY Mild anemia with microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X has not been found except in a minor Hb zone isolated by CM-cellulose chromatography CHROMATOGRAPHY None reported STRUCTURE STUDIES Not reported DNA ANALYSES An AGG->ACG mutation at codon 30; codon 30 (AGG) is divided by intron 1 as follows: ---CTT*AGG*CTG*CTG---. It is the last nt G of exon 1 that is changed to C FUNCTION STUDIES Not reported STABILITY Most unstable OCCURRENCE Found in a Black family and a North African woman born to a Libyan father and a Tunisian mother OTHER INFORMATION Found in a Black girl in combination with the promoter mutation A->G at position -29; this patient was transfusion dependent REFERENCES 1. Gonzalez-Redondo, J.M., Stoming, T.A., Kutlar, F., Kutlar, A., Hu, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 13:67, 1989. 2. Vidaud, M., Gattoni, R., Stevenin, J., Vidaud, D., Amselem, S., Chibani, J., Rosa, J., and Goossens, M.: Proc. Natl. Acad. Sci. USA, 86:1041, 1989. Hb Yokohama beta31(B13)Leu->Pro CONTACT Heme contact; internal residue HEMATOLOGY Severe hemolytic anemia in the heterozygote; Heinz bodies ELECTROPHORESIS Hb X and Hb A do not separate at alkaline pH; no separation by IEF CHROMATOGRAPHY No separation obtained; the betaX chain elutes ahead of the betaA chain in the reversed phase HPL chromatogram STRUCTURE STUDIES The betaX chain was isolated by pCMB precipitation; proteolytic digestion; separation of peptides by reversed phase HPLC; fingerprinting; amino acid analysis; sequencing DNA ANALYSES A CTG->CCG mutation at codon 31 (Ref. 2) FUNCTION STUDIES Slightly decreased oxygen affinity STABILITY Unstable OCCURRENCE Found in members of a Japanese family and in a Serbian teenager OTHER INFORMATION Quantity in heterozygotes not definitely determined; a de novo mutation REFERENCES 1. Nakatsuji, T., Miwa, S., Ohba, Y., Hattori, Y., Miyaji, T., Hino, S., and Matsumoto, N.: Hemoglobin, 5:667, 1981. 2. Plaseska, D., Jankovic, L., Dimovski, A.J., Milenovic, D., Juricic, D., and Efremov, G.D.: Hemoglobin, 15:469, 1991. Hb Hakkari beta31(B13)Leu->Arg CONTACT Heme contact; internal residue HEMATOLOGY Severe hemolytic anemia in the heterozygote ELECTROPHORESIS No abnormal Hb detected CHROMATOGRAPHY No abnormal Hb detected; no abnormal beta chain detected by reversed phase HPLC STRUCTURE STUDIES Not possible DNA ANALYSES A CTG->CGG mutation at codon 31 FUNCTION STUDIES Not performed STABILITY Severely unstable; abnormal Hb is observed as inclusion bodies in erythroblasts OCCURRENCE Found in a young Turkish child OTHER INFORMATION A de novo mutation REFERENCES 1. Gurgey, A., Altay, C., Gu, L-H., Leonova, J.Ye., Delibalta, A., Oner, C., and Huisman, T.H.J.: Hemoglobin, 19:165, 1995. Hb Perth beta32(B14)Leu->Pro ALSO KNOWN AS Abraham Lincoln; Kobe CONTACT Internal HEMATOLOGY Congenital hemolytic anemia with reticulocytosis in the heterozygote ELECTROPHORESIS No separation observed CHROMATOGRAPHY No separation observed STRUCTURE STUDIES The betaX chain was precipitated with pCMB; tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTG->CCG at codon 32 FUNCTION STUDIES Normal oxygen affinity STABILITY Unstable OCCURRENCE Found in an Australian male, a Black female from New Orleans, a severely anemic Hottentot male from South Africa, and a French male but not in his parents OTHER INFORMATION De novo mutations REFERENCES 1. Jackson, J.M., Yates, A., and Huehns, E.R.: Br. J. Haematol., 25:607, 1973. 2. Honig, G.R., Green, D., Shamsuddin, M., Vida, L.N., Mason, R.G., Gnarra, D.J., and Maurer, H.S.: J. Clin. Invest., 52:1746, 1973. 3. Grove, S.S., Jenkins, T., Kamuzora, H.L., and Lehmann, H.: Acta Haematol., 57: 143, 1977. Hb Castilla beta32(B14)Leu->Arg CONTACT Internal HEMATOLOGY Hemolytic anemia with reticulocytosis in the heterozygote; Heinz bodies ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves to the position of Hb S CHROMATOGRAPHY Not performed STRUCTURE STUDIES The betaX chain was isolated with pCMB; tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG at codon 32 FUNCTION STUDIES Not performed STABILITY Unstable OCCURRENCE Found in a Spanish female OTHER INFORMATION A de novo mutation; quantity in the heterozygote ~22% REFERENCES 1. Garel, M.C., Blouquit, Y., and Rosa, J.: FEBS Lett., 58:145, 1975. Hb Muscat beta32(B14)Leu->Val CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A do not separate at alkaline pH; no separation by IEF CHROMATOGRAPHY No separation of Hb X and Hb A; the betaX chain elutes ahead of betaA on a reversed phase HPLC column STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTG->GTG at codon 31 FUNCTION STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found in an Arabian family from Muscat, Oman OTHER INFORMATION One member of the family had Hb S combined with Hb Muscat; betaX = 47.5% and betaS = 52.5%; in the heterozygote: betaA = 58.5%; betaX = 41.5% REFERENCES 1. Ramachandran, M., Gu, L-H., Wilson, J.B., Kitundu, M.N., Adekile, A.D., Liu, J-C., McKie, K.M., and Huisman, T.H.J.: Hemoglobin, 16:259, 1992. Hb Pitie-Salpetriere beta34(B16)Val->Phe CONTACT alpha1beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote; reticulocytosis ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; in IEF Hb X moves cathodally to Hb A and adjacent to Hb F CHROMATOGRAPHY Not performed STRUCTURE STUDIES Proteolytic digestion; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTC->TTC at codon 34 FUNCTION STUDIES Increased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a French family OTHER INFORMATION Quantity in the heterozygote 36-38% REFERENCES 1. Blouquit, Y., Braconnier, F., Cohen-Solal, M., Foldi, J., Arous, N., Ankri, A., Binet, J.L., and Rosa, J.: Biochim. Biophys. Acta, 624:473, 1980. Hb Philly beta35(C1)Tyr->Phe CONTACT alpha1beta1 contact HEMATOLOGY Chronic hemolytic anemia in the heterozygote; reticulocytosis ELECTROPHORESIS No separation at alkaline pH; Hb X has a slightly higher pI than Hb A in IEF CHROMATOGRAPHY No separation reported STRUCTURE STUDIES The betaX chain was isolated with pCMB; tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation TAC->TTC at codon 35 FUNCTION STUDIES Increased oxygen affinity and IHP effect; decreased cooperativity and 2,3-DPG effect STABILITY Unstable OCCURRENCE Found in members of an Italian-German-French family OTHER INFORMATION Quantity in heterozygotes 30-35% REFERENCES 1. Rieder, R.F., Oski, F.A., and Clegg, J.B.; J. Clin. Invest., 48:1627, 1969. 2. Asakura, T., Adachi, K., Wiley, J.S., Fung, L.W-M., Ho, C., Kilmartin, J.V., and Perutz, M.F.: J. Mol. Biol., 104:185, 1976. Hb Linkoping beta36(C2)Pro->Thr ALSO KNOWN AS Meilahti; Finlandia CONTACT alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A observed at alkaline pH CHROMATOGRAPHY No separation observed by cation exchange HPLC; the betaX chain elutes very slowly from a reversed phase HPLC column (slower than the gamma chains) STRUCTURE STUDIES Mass spectrometry; amino acid sequence analysis DNA ANALYSES A CCT->ACT mutation at codon 36 (Ref. 3) FUNCTION STUDIES Increased oxygen affinity STABILITY Mildly unstable OCCURRENCE Found in several Finnish families and in a female of Dutch descent OTHER INFORMATION Quantity in the heterozygote about 30% REFERENCES 1. Jeppsson, J-O., Kallman, L., Lindgren, G., and Fagerstam, L.G.: J. Chromatogr., 297:31, 1984. 2. Jones, R.T., Head, C., Shih, M.F-C., Shih, D.T-B., Dana, B., Jones, M.B., and Koler, R.D.: Hemoglobin, 10:455, 1986. 3. Ward, C.M., Fay, K.C., Brennan, J., Lowrey, I., and Blacklock, H.A.: Aust. N.Z. J. Med., 22:390, 1992. Hb North Chicago beta36(C2)Pro->Ser CONTACT alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; separation is possible by IEF; excellent separation of betaX, betaA, and alpha by PAGE CHROMATOGRAPHY No separation reported; the betaX chain elutes after the normal alpha chain from a reversed phase HPLC column STRUCTURE STUDIES Tryptic digestion of the betaX chain; separation of the peptides by fingerprinting and by reversed phase HPLC; amino acid analysis; ion mass spectral analysis DNA ANALYSES Not reported; presumed mutation CCT->TCT at codon 36 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Discovered in members of a Black family OTHER INFORMATION None REFERENCES 1. Rahbar, S., Louis, J., Lee, T., and Asmerom, Y.: Hemoglobin, 9:559, 1985. Hb Sunnybrook beta36(C2)Pro->Arg CONTACT alpha1beta2 contact HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X was easily separated from Hb A by alkaline electrophoresis with a mobility slightly faster than Hb S; did not separate from Hb A by agar gel electrophoresis CHROMATOGRAPHY Hb X moves like Hb E in cation exchange HPLC; does not separate from Hb A2; Hb X elutes between Hb A2 and Hb A on DEAE-cellulose chromatography; the betaX chain separates from the betaA and alpha chains by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of the peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCT->CGT at codon 36 FUNCTION STUDIES Increased oxygen affinity; slightly altered Bohr effect STABILITY Not reported OCCURRENCE Found in a male of European descent OTHER INFORMATION Quantity in the heterozygote ~35% REFERENCES 1. Ali, M.A.M., Pinkerton, P., Chow, S.W.S., Zaetz, S.D., Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 12:137, 1988. Hb Hirose beta37(C3)Trp->Ser CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb F at alkaline pH CHROMATOGRAPHY Hb X was isolated by CM-cellulose chromatography; Hb X elutes between Hb A and Hb A2 STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; specific staining for tryptophan DNA ANALYSES Not reported; presumed mutation TGG->TCG at codon 37 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in a few Japanese families OTHER INFORMATION Quantity in the heterozygote 41.4%; dissociates into dimers in the liganded state REFERENCES 1. Yamaoka, K.: Blood, 38:730, 1971. 2. Fujita, S.: J. Clin. Invest., 51:2520, 1972. 3. Ohba, Y., Hattori, Y., Fuyuno, K., Takeda, I., Matsuoka, M., Yoshinaka, H., Satoh, T., and Miyaji, T.: Hemoglobin, 7:191, 1983. Hb Rothschild beta37(C3)Trp->Arg CONTACT alpha1beta2 contact HEMATOLOGY Nearly normal in the heterozygote; slight increase in reticulocytes ELECTROPHORESIS Hb X and Hb A separate at both alkaline and acidic pH; Hb X moves between Hb A2 and Hb S at high pH; it moves like Hb S at low pH; excellent separation by IEF CHROMATOGRAPHY Hb X separates from Hb A by anion exchange chromatography; elution order: A2-X-A STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGG->AGG or CGG at codon 37 FUNCTION STUDIES Decreased oxygen affinity and cooperativity STABILITY Normal OCCURRENCE Found in a few Caucasian families OTHER INFORMATION Quantity in the heterozygote 37-50%; dissociates into dimers in the liganded state REFERENCES 1. Gacon, G., Belkhodja, O., Wajcman, H., and Labie, D.: FEBS Lett., 82:243, 1977. 2. Craik, C.S., Vallette, I., Beychok, S., and Waks, M.: J. Biol. Chem., 255:6219, 1980. 3. Danish, E.H., Harris, J.W., Ahmed, F., and Anderson, H.: Hemoglobin, 6:51, 1982. Hb Howick beta37(C3)Trp->Gly CONTACT alpha1beta2 contact HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at both alkaline and acidic pH; Hb X moves like Hb S or Hb D at high pH, and like Hb F at low pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TGG->GGG at codon 37 FUNCTION STUDIES Slightly increased oxygen affinity; reduced Bohr effect STABILITY Normal OCCURRENCE Found in one adult of unnamed racial or ethnic background OTHER INFORMATION Quantity in the heterozygote 29% REFERENCES 1. Owen, M.C., Ockelford, P.A., and Wells, R.M.G.: Hemoglobin, 17:513, 1993. Hb Hazebrouck beta38(C4)Thr->Pro CONTACT Heme contact HEMATOLOGY Hemolytic anemia with reticulocytosis; Heinz bodies ELECTROPHORESIS Not detectable with standard methodology; Hb X moves slightly slower than Hb A by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; fingerprinting and reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation ACC->CCC at codon 38 FUNCTION STUDIES Decreased oxygen affinity STABILITY Mildly unstable OCCURRENCE Observed in a French male OTHER INFORMATION Quantity in the heterozygote estimated at 31%; hemichrome formation REFERENCE 1. Blouquit, Y., Delanoe-Garin, J., Lacombe, C., Arous, N., Cayre, Y., Peduzzi, J., Braconnier, F., and Galacteros, F.: FEBS Lett., 172, 155, 1984. Hb Alabama beta39(C5)Gln->Lys CONTACT alpha1beta2 contact HEMATOLOGY Mild anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves to the position of Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography; Hb X elutes between Hb A and Hb A2 STRUCTURE STUDIES Tryptic digestion; cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAG->AAG at codon 39 FUNCTION STUDIES Not performed STABILITY Not performed OCCURRENCE Found in a Black family from Alabama, USA OTHER INFORMATION Quantity in the heterozygote 38% REFERENCES 1. Brimhall, B., Jones, R.T., Schneider, R.G., Hosty, T.S., Tomlin, G., and Atkins, R.: Biochim. Biophys. Acta, 379:28, 1975. Hb Vaasa beta39(C5)Gln->Glu CONTACT alpha1beta2 contact HEMATOLOGY Mild hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves to a position slightly faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography; Hb X elutes approximately as Hb F STRUCTURE STUDIES Tryptic digestion of betaX chain; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAG->GAG at codon 39 FUNCTION STUDIES Not performed STABILITY Slightly unstable OCCURRENCE Found in members of a Finnish family OTHER INFORMATION Quantity in the heterozygote 33.1% REFERENCES 1. Kendall, A.G., ten Pas, A., Wilson, J.B., Cope, N., Bolch, K., and Huisman, T.H.J.: Hemoglobin, 1:292, 1977. Hb Tianshui beta39(C5)Gln->Arg CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X takes the position of Hb G and moves slightly faster than Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAG->CGG at codon 39 FUNCTION STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in a Chinese (Han) family OTHER INFORMATION Quantity in the heterozygote 41% REFERENCES 1. Li, H.J., Zhao, X.N., Li, H.W., Li, L., Liang, K.X., Wang, R.P., Chang, T.T., Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 14:569, 1990. Hb Athens-GA beta40(C6)Arg->Lys ALSO KNOWN AS Waco CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH and by IEF; Hb X moves slightly slower than Hb A CHROMATOGRAPHY Hb X and Hb A were separated by both cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; peptides separated by cation exchange chromatography or reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGG->AAG at codon 40 FUNCTION STUDIES Increased oxygen affinity; Bohr effect and cooperativity normal STABILITY Normal OCCURRENCE Found in a few Caucasian families in the Southeastern USA OTHER INFORMATION Quantity in the heterozygote 47.4-51.4% REFERENCES 1. Brown, W.J., Niazi, G.A., Jayalakshmi, M., Abraham, E.C., and Huisman, T.H.J.: Biochim. Biophys. Acta, 439:70, 1976. 2. Moo-Penn, W.F., Johnson, M.H., Bechtel, K.C., Jue, D.L., Therrell, B.L., Jr., and Schmidt, R.M.: Arch. Biochem. Biophys., 179:86, 1977. Hb Austin beta40(C6)Arg->Ser CONTACT alpha1beta2 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb A and Hb F at both alkaline and acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography and reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AGG->AGC or AGT at codon 40 FUNCTION STUDIES Increased oxygen affinity; reduced cooperativity; normal Bohr effect STABILITY Stable; dissociation into dimers when oxygenated OCCURRENCE Found in three unrelated individuals of Mexican ancestry OTHER INFORMATION Quantity in the heterozygote 45% REFERENCES 1. Moo-Penn, W.F., Johnson, M.H., Bechtel, K.C., Jue, D.L., Therrell, B.L., Jr., and Schmidt, R.M.: Arch. Biochem. Biophys., 179:86, 1977. Hb Mequon beta41(C7)Phe->Tyr CONTACT Heme contact HEMATOLOGY Severe hemolytic crisis during viral infection; treated with acetaminophen; Heinz bodies present at this time; past general health excellent; macrocytosis and reticulocytosis ELECTROPHORESIS No separation reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TTC->TAC at codon 41 FUNCTION STUDIES Normal STABILITY Unstable OCCURRENCE Found in a female of English-Irish extraction OTHER INFORMATION Quantity in the heterozygote ~40-50% by amino acid analysis REFERENCES 1. Burkert, L.B., Sharma, V.S., Pisciotta, A.V., Ranney, H.M., and Bruckheimer, S.: Blood, 48:645, 1976. Hb Denver beta41(C7)Phe->Ser CONTACT Heme contact HEMATOLOGY Normal to mild anemia in the heterozygote; cyanosis ELECTROPHORESIS No separation obtained at alkaline pH or by IEF CHROMATOGRAPHY No separation reported STRUCTURE STUDIES No details reported DNA ANALYSES Not reported; presumed mutation TTC->TCC at codon 41 FUNCTION STUDIES Decreased oxygen affinity STABILITY Unstable OCCURRENCE Found in members of a Caucasian family OTHER INFORMATION None; quantity in the heterozygote not determined REFERENCES 1. Stabler, S., Jones, R.T., Head, C, Shih, D.T.B., and Fairbanks, V.F.: Blood, 82: 229a (Suppl. 1), 1993. Hb Hammersmith beta42(CD1)Phe->Ser ALSO KNOWN AS Chiba CONTACT Heme contact HEMATOLOGY Severe Heinz body hemolytic anemia ELECTROPHORESIS No clear separations obtained in any medium CHROMATOGRAPHY No separation by cation or anion exchange HPLC; excellent separation of betaX and betaA chains by reversed phase HPLC; betaX elutes ahead of betaA STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; chymotryptic digestion; sequencing DNA ANALYSES A TTT->TCT mutation at codon 42 (Ref. 3) FUNCTION STUDIES Decreased oxygen affinity and cooperativity STABILITY Unstable OCCURRENCE Found in a few English children, a Japanese male, and in an North American Indian OTHER INFORMATION Routine blood transfusions required; splenectomy helpful; quantity in the heterozygote (before transfusion) ~23% REFERENCES 1. Dacie, J.V., Shinton, N.K., Gaffney, P.J., Jr., Carrell, R.W., and Lehmann, H.: Nature, 216:663, 1967. 2. May, A. and Huehns, E.R.: Br. J. Haematol., 30:185, 1975. 3. Cunningham, T.A., Baker, F., Kobrinsky, N.L., Cepreganova, B., Baysal, E., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 16:19, 1992. Hb Louisville beta42(CD1)Phe->Leu ALSO KNOWN AS Bucuresti CONTACT Heme contact HEMATOLOGY Mild hemolytic anemia with reticulocytosis; Heinz bodies ELECTROPHORESIS No separations reported CHROMATOGRAPHY No separations reported STRUCTURE STUDIES The betaX chain was isolated by pCMB precipitation; tryptic digestion; separation of peptides by cation exchange chromatography; sequencing DNA ANALYSES Not reported; presumed mutation TTT->CTT at codon 42 FUNCTION STUDIES Decreased oxygen affinity and cooperativity; normal Bohr effect STABILITY Unstable OCCURRENCE Found in members of a family of English-Irish ancestry living in Kentucky, USA; a Rumanian woman and her daughter; in several members of a Cuban family, and in a Canadian female OTHER INFORMATION None REFERENCES 1. Keeling, M.M., Ogden, L.L., Wrightstone, R.N., Wilson, J.B., Reynolds, C.A., Kitchens, J.L., and Huisman, T.H.J.: J. Clin. Invest., 50:2395, 1971. 2. Bratu, V., Lorkin, P.A., Lehmann, H., and Predescu, C.: Biochim. Biophys. Acta, 251:1, 1971. 3. Colombo, B., Benitez, M.P., Bernini, L., Elion, J., Wajcman, H., and Labie, D.: J. Med. Genet., 12:297, 1975. 4. Gravely, M.E., Wilson, J.B., Huisman, T.H.J., and Smiley, R.K.: Hemoglobin, 2:89, 1978. Hb Sendagi beta42(CD1)Phe->Val ALSO KNOWN AS Warsaw CONTACT Heme contact HEMATOLOGY Moderate hemolytic anemia with reticulocytosis; Heinz bodies ELECTROPHORESIS No separation reported CHROMATOGRAPHY No separation by cation or anion exchange chromatography; betaX elutes ahead of betaA in reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TTT->GTT at codon 42 FUNCTION STUDIES Decreased oxygen affinity STABILITY Unstable OCCURRENCE Found in a Japanese male and his daughter, and in a Polish-American family OTHER INFORMATION Quantity in heterozygotes estimated at 42-45% (reversed phase HPLC); metHb formation REFERENCES 1. Ogata, K., Ito, T., Kazaki, T., Dan, K., Nomura, T., Nozawa, Y., and Kajita, A.: Hemoglobin, 10:469, 1986. 2. Honig, G.R., Telfer, M.C., Rosenblum, B.B., and Vida, L.N.: Am. J. Hematol., 32:36, 1989. 3. Honig, G.R., Vida, L.N., Rosenblum, B.B., Perutz, M.F., and Fermi, G.: J. Biol. Chem., 265:126, 1990. Hb G-Galveston beta43(CD2)Glu->Ala ALSO KNOWN AS G-Port Arthur; G-Texas CONTACT External HEMATOLOGY Normal in heterozygotes ELECTROPHORESIS Hb X and Hb A separate at alkaline pH where Hb G is slightly faster than Hb S, and at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GCG at codon 43 FUNCTION STUDIES Normal STABILITY Not reported OCCURRENCE Found in a few Black families, including a homozygote; a father and nine children; a mother and five children, and a Black male with a compound heterozygosity for Hb G and Hb S OTHER INFORMATION Quantity in heterozygotes 50%; the homozygote is healthy REFERENCES 1. Edington, G.M., Lehmann, H., and Schneider, R.G.: Nature, 175:850, 1955. 2. Bowman, B.H., Moreland, H., and Schneider, R.G.: Nature, 193:1298, 1960. 3. McCurdy, P.R., Lorkin, P.A., Casey, R., Lehmann, H., Uddin, D.E., and Dickson, L.G.: Am. J. Med., 57:665, 1974. Hb Hoshida beta43(CD2)Glu->Gln ALSO KNOWN AS Chaya CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH and by IEF; Hb X is slightly faster than Hb S CHROMATOGRAPHY Hb X and Hb A separate in anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; reversed phase HPLC; chymotryptic and thermolysin digestion; amino acid analysis; sequencing DNA ANALYSES A GAG->CAG mutation at codon 43 (Ref. 2) FUNCTION STUDIES Normal STABILITY Stable OCCURRENCE Found in a Japanese family and in a Yugoslavian family OTHER INFORMATION Quantity in the heterozygote 42-45% REFERENCES 1. Iuchi, I., Ueda, S., Hidaka, K., and Shibata, S.: Hemoglobin, 2:235, 1978. 2. Plaseska, D., Dimovski, A.J., Jankovic, L., Sukarova, E., Efremov, G.D., Gebauer, E., and Jerance, D.: Hemoglobin, 15:541, 1991. Hb Mississippi beta44(CD3)Ser->Cys CONTACT Heme contact HEMATOLOGY Normal in the heterozygote; Heinz body formation after oxidant stress ELECTROPHORESIS More than one Hb zone might be present; three abnormal bands observed in globin chain electrophoresis CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation TCC->TGC at codon 44 FUNCTION STUDIES Not reported STABILITY Mildly unstable; formation of high molecular weight multi-mers (with other chains) OCCURRENCE Found in a Chinese family OTHER INFORMATION Occurs together with an undefined, presumably beta+-thal in the proband, causing a phenotype of thalassemia intermedia REFERENCES 1. Steinberg, M.H., Adams, J.G., III, Morrison, W.T., Pullen, D.J., Abney, R., Ibrahim, A., and Rieder, R.F.: J. Clin. Invest., 79:826, 1987. Hb Cheverly beta45(CD4)Phe->Ser CONTACT Heme contact HEMATOLOGY Mild chronic hemolytic anemia with reticulocytosis; Heinz bodies ELECTROPHORESIS No separation of Hb X and Hb A at alkaline and acidic pH CHROMATOGRAPHY Not reported; the betaX and betaA chains will likely separate by reversed phase HPLC STRUCTURE STUDIES Fingerprinting; HPLC; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TTT->TCT at codon 45 FUNCTION STUDIES Decreased oxygen affinity; reduced Bohr effect STABILITY Unstable OCCURRENCE Found in an Italian male and a Caucasian family OTHER INFORMATION Quantity in the heterozygote 24-40% REFERENCES 1. Sciarratta, G.V., Sansone, G., Valbonesi, M., Wilson, J.B., Lam, H., Webber, B.B., Headlee, M.E., and Huisman, T.H.J.: Hemoglobin, 6:419, 1982. 2. Yeager, A.M., Zinkham, W.H., Jue, D.L., Winslow, R.M., Johnson, M.H., McGuffey, J.E., and Moo-Penn, W.F.: Pediatr. Res., 17:503, 1983. Hb Arta beta45(CD4)Phe->Cys CONTACT Heme contact HEMATOLOGY Probably normal in the heterozygote; the proband is a compound heterozygote with betao-thal (codon 39, C->T); she has a moderate anemia with reticulocytosis; Heinz bodies ELECTROPHORESIS No separation at alkaline pH or by IEF; citrate agar electrophoresis at pH 6 shows "a band slower than Hb A" CHROMATOGRAPHY Not reported; the betaX chain elutes earlier than the betaA chain in reversed phase HPLC STRUCTURE STUDIES "confirmatory of a Phe->Cys mutation at codon 45" DNA ANALYSES A TTT->TGT mutation at codon 45 FUNCTION STUDIES Decreased oxygen affinity STABILITY Unstable OCCURRENCE Observed in a Greek family OTHER INFORMATION None REFERENCES 1. Vassilopoulos, G., Papassotiriou, J., Voskaridou, E., Stamoulakatou, A., Premetis, E., Galacteros, F., Wajcman, H., and Loukopoulos, D.: Abstract 255, Br. J. Haematol., 87 (Suppl. 1), 1994. 2. Papassotiriou, I., Kister, J., Marden, M., Griffon, N., Wajcman, H., Stamoulakaatou, A., Loukopoulos, D., and Poyart, C.: Abstract 47, Nouv. Rev. Fr. d'Hematol., 38:27, 1996. Hb K-Ibadan beta46(CD5)Gly->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH; no separation at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting or reversed phase HPLC for peptide separation; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGG->GAG at codon 46 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in an African Yoruba adolescent and in an Italian family OTHER INFORMATION Quantity in the heterozygote 28-33% REFERENCES 1. Allan, N., Beale, D., Irvine, D., and Lehmann, H.: Nature, 208:658, 1965. 2. Castagnola, M., Cassiano, L., Rossetti, D.V., Marucci, L., Ferro, A., Scarano, C., Monaco, M., and Celozzi, A.M.: Hemoglobin, 14:647, 1990. Hb Gainesville-GA beta46(CD5)Gly->Arg CONTACT External HEMATOLOGY Observed in two healthy newborn babies; data from heterozygous parents not available ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (it moves as Hb S) but not at acidic pH CHROMATOGRAPHY Originally isolated by DEAE-cellulose chromatography; also excellent separations by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGG->AGG at codon 46 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a few Black newborns living in North Georgia OTHER INFORMATION Quantity in the heterozygote 36-37% REFERENCES 1. Chen, S.S., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 9: 179, 1985. 2. Wilson, J.B., Webber, B.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 13: 623, 1989. Hb G-Copenhagen beta47(CD6)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves slightly ahead of Hb S) but not at acidic pH CHROMATOGRAPHY Excellent separation of Hb X and Hb A by cation exchange HPLC and DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; peptides separated by reversed phase HPLC or by fingerprinting; amino acid analysis; chymotryptic digestion; sequencing DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 47 FUNCTION STUDIES Not reported STABILITY Stable OCCURRENCE Found in a Danish, a Sicilian, and a Black family OTHER INFORMATION Quantity in the heterozygote 46-48% REFERENCES 1. Sick, K., Beale, D., Irvine, D., Lehmann, H., Goodall, P.T., and MacDougall, S.: Biochim. Biophys. Acta, 140:231, 1967. 2. Schiliro, G., Musumeci, S., Russo, A., Marino, S., Russo, G., Marinucci, M., Fontanarosa, P.P., and Tentori, L.: Hemoglobin, 5:195, 1981. 3. Chen, S.S., Wilson, J.B., Webber, B.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 9:405, 1985. Hb Gavello beta47(CD6)Asp->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves as Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; chymotryptic digestion DNA ANALYSES Not reported; presumed mutation GAT->GGT at codon 47 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 79-year-old female of North Italian origin OTHER INFORMATION Quantity in the heterozygote 42% REFERENCES 1. Marinucci, M., Mavilio, F., Tentori, L., and Alberti, R.: Hemoglobin, 1:771, 1977. Hb Avicenna beta47(CD6)Asp->Ala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at both alkaline and acidic pH; Hb X moves like Hb S at pH 8.5 and 6.2 CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; thermolytic digestion DNA ANALYSES Not reported; presumed mutation GAT->GCT at codon 47 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a young Iranian male OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Rahbar, S., Nozari, G., and Ala, F.: Biochim. Biophys. Acta, 576:466, 1979. Hb Maputo beta47(CD6)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves in the position of Hb S) but not at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; reversed phase HPLC; fingerprinting; amino acid analysis; LAP DNA ANALYSES Not reported; presumed mutation GAT->TAT at codon 47 FUNCTION STUDIES Normal oxygen affinity and cooperativity STABILITY Normal OCCURRENCE Found in members of a family from Mozambique and in two Caucasian families in the USA OTHER INFORMATION Quantity in the heterozygote 30.1%; also found in combination with Hb S REFERENCES 1. Marinucci, M., Boissel, J.P., Massa, A., Wajcman, H., Tentori, L., and Labie, D.: Hemoglobin, 7:423, 1983. 2. Moo-Penn, W.F., Hine, T.K., Johnson, M.H., Jue, D.L., Piersma, H., Therrell, B., Jr., and Chu, A.: Hemoglobin, 15:97, 1991. Hb Okaloosa beta48(CD7)Leu->Arg CONTACT External HEMATOLOGY Normal in the heterozygote; mild reticulocytosis ELECTROPHORESIS Hb X and Hb A separate well at alkaline pH (Hb X moves in the position of Hb S) but not at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG at codon 48 FUNCTION STUDIES Decreased oxygen affinity; Bohr effect and cooperativity normal; increased 2,3-DPG effect STABILITY Unstable OCCURRENCE Found in six members of a Caucasian family living in Florida, USA OTHER INFORMATION Quantity in the heterozygote 32-36% REFERENCES 1. Charache, S., Brimhall, B., and Milner, P.: J. Clin. Invest., 52:2858, 1973. Hb Bab-Saadoum beta48(CD7)Leu->Pro CONTACT External HEMATOLOGY Mild anemia with reticulocytosis ELECTROPHORESIS No separation with standard methodology; Hb X and Hb A focus closely together in IEF CHROMATOGRAPHY Hb X and Hb A separate incompletely by cation exchange HPLC; the betaX and betaA chains readily separate by reversed phase HPLC; betaX elutes ahead of betaA STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CCG at codon 48 FUNCTION STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in a Tunisian boy but not in his parents OTHER INFORMATION Quantity in the heterozygote 25.8% (betaX as % of betaX+betaA) REFERENCES 1. Molchanova, T.P., Wilson, J.B., Gu, L-H., Guemira, F., Fattoum, S., and Huisman, T.H.J.: Hemoglobin, 16:267, 1992. Hb Las Palmas beta49(CD8)Ser->Phe CONTACT External HEMATOLOGY Normal in the heterozygote; mild reticulocytosis ELECTROPHORESIS No separation by standard techniques; the betaX and betaA chains separate by PAGE CHROMATOGRAPHY No separation by cation or anion exchange HPLC; the betaX and betaA chains separate in reversed phase HPLC; betaX elutes very slowly behind alpha (betaA, alpha, betaX) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TCC->TTC at codon 49 FUNCTION STUDIES Not determined STABILITY Slightly unstable OCCURRENCE Found in two members of a family from the Canary Islands, Spain OTHER INFORMATION Quantity in the heterozygote 43-45% REFERENCES 1. Malcorra-Azpiazu, J.J., Balda-Aguirre, M.I., Diaz-Chico, J.C., Hu, H., Wilson, J.B., Webber, B.B., Kutlar, F., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 12:163, 1988. Hb Edmonton beta50(D1)Thr->Lys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves in the position of Hb S) but not at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation ACT->[AAA or AAG] at codon 50 (see below) FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Canadian male of Ukrainian origin OTHER INFORMATION Quantity in the heterozygote 20% (probably too low); prior to the mutation the codon at beta50 likely was ACA (->AAA) or ACG (->AAG) rather than the listed ACT REFERENCES 1. Labossiere, A., Hill, J.R., and Vella, F.: Clin. Biochem., 4:114, 1971. Hb Willamette beta51(D2)Pro->Arg CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote except for target cells; hypochromia ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X occupies a position as Hb S) and incompletely at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCT->CGT at codon 51 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect; normal cooperativity; normal oxygen affinity and Bohr effect in the absence of phosphates STABILITY Mildly unstable OCCURRENCE Found in members of a few Black families OTHER INFORMATION Quantity in the heterozygote ~35% REFERENCES 1. Jones, R.T., Koler, R.D., Duerst, M.L., and Dhindra, D.S.: Hemoglobin, 1:45, 1977. 2. Quarum, M., Shih, T-B., and Jones, R.T.: Hemoglobin, 7:57, 1983. 3. Martinez, G., Canizares, M.E., and Colombo, B.: Hemoglobin, 8:193, 1984. Hb Osu-Christiansborg beta52(D3)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X in the position of Hb S) but not at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by anion and cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; thermolysin digestion; sequencing DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 52 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in members of a family living in Accra, Ghana, in an Iranian family, and in Blacks in the USA OTHER INFORMATION Quantity in the heterozygote 42-45%; also found in combination with Hb S REFERENCES 1. Konotey-Ahulu, F.I.D., Kinderlerer, J.L., Lehmann, H., and Ringelhann, B.: J. Med. Genet., 3:302, 1977. 2. Rahbar, S., Mostafavi, I., and Ala, F.: Hemoglobin, 2:175, 1978. Hb Ocho Rios beta52(D3)Asp->Ala CONTACT External HEMATOLOGY Normal in the heterozygote; a few target cells ELECTROPHORESIS Hb X and Hb A can be separated at alkaline and acidic pH; Hb X moves like Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; chymotryptic digestion DNA ANALYSES Not reported; presumed mutation GAT->GCT at codon 52 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Black Jamaican male OTHER INFORMATION Found in association with Hb S REFERENCES 1. Beresford, C.H., Clegg, J.B., and Weatherall, D.J.: J. Med. Genet., 9:151, 1972. Hb Summer Hill beta52(D3)Asp->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X in the position of Hb S) CHROMATOGRAPHY Hb X and Hb A separate in anion and cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC or fingerprinting; amino acid analysis; thermolysin digestion DNA ANALYSES Not reported; presumed mutation GAT->CAT at codon 52 FUNCTION STUDIES Normal oxygen affinity, Bohr effect, cooperativity, and 2,3-DPG STABILITY Normal OCCURRENCE Found in a Lebanese female living in New South Wales, Australia, and in a Turkish family from Northern Cyprus OTHER INFORMATION Quantity in the heterozygote 32.5-44.5% REFERENCES 1. Wilkinson, T., Brennan, S.O., Carrell, R.W., Wells, R.M., Como, P., and Kronen-berg, H.: Hemoglobin 4:185, 1980. 2. Cin, S., Akar, N., Cavdar, A.O., Arcasoy, A., Dedeoglu, S., Webber, B., Lam, H., and Huisman, T.H.J.: Hemoglobin, 7:467, 1983. Hb Jacksonville beta54(D5)Val->Asp CONTACT Internal HEMATOLOGY Hemolytic anemia with reticulocytosis, mainly during infections; inclusion bodies ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves between Hb A and Hb J) CHROMATOGRAPHY Hb X and Hb A separate by DEAE-Sephadex chromatography; the betaX chain elutes ahead of the betaA chain by reversed phase HPLC STRUCTURE STUDIES The AE-betaX chain was digested with trypsin; peptides were separated by fingerprinting; amino acid analysis; sequencing with an automated sequencer DNA ANALYSES Not reported; presumed mutation GTT->GAT at codon 54 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Unstable OCCURRENCE Found in a Black teenager OTHER INFORMATION Quantity in the heterozygote ~37%; the parents are normal REFERENCES 1. Gaudry, C.L., Jr., Pitel, P.A., Jue, D.L., Hine, T.K., Johnson, M.H., and Moo-Penn, W.F.: Hemoglobin, 14:653, 1990. Hb Matera beta55(D6)Met->Lys CONTACT alpha1beta1 contact HEMATOLOGY Normal in the heterozygote; inclusion bodies ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X occupies a position like Hb S; excellent separation by IEF; no separation at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation ATG->AAG at codon 55 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in four members of an Italian family OTHER INFORMATION Quantity in the heterozygote 34-38% REFERENCES 1. Sciarratta, G.V. and Ivaldi, G.: Hemoglobin, 14:79, 1990. Hb J-Bangkok beta56(D7)Gly->Asp ALSO KNOWN AS J-Meinung; J-Korat; J-Manado CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; CNBr; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGC->GAC at codon 56 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in Thai, Indonesian, Black, and Chinese families OTHER INFORMATION Quantity in the heterozygote 40-45%; also found in combination with Hb S REFERENCES 1. Clegg, J.B., Naughton, M.A., and Weatherall, D.J.: J. Mol. Biol., 19:91, 1966. 2. Blackwell, R.Q. and Liu, C-S.: Biochem. Biophys. Res. Commun., 24:732, 1966. 3. Pootrakul, S., Wasi, P., and Na-Nakorn, S.: Br. J. Haematol., 13:303, 1967. Hb Hamadan beta56(D7)Gly->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X occupies the position of Hb S) CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC at codon 56 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in three members of an Iranian family, a French Caucasian family, and in four members of a family of Turkish descent OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Rahbar, S., Nowzari, G., Haydari, H., and Daneshmand, P.: Biochim. Biophys. Acta, 379:645, 1975. 2. Dincol, G., Aksoy, M., Dincol, K., Kutlar, A., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 8:423, 1984. Hb G-Ferrara beta57(E1)Asn->Lys CONTACT External HEMATOLOGY Data for the heterozygote not reported ELECTROPHORESIS Not reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->AAA or AAG at codon 57 FUNCTION STUDIES Normal oxygen affinity, alkaline Bohr effect, and cooperativity STABILITY Mildly unstable OCCURRENCE Found in one Italian family OTHER INFORMATION Present in combination with a beta-thal determinant REFERENCES 1. Tentori, L.: Abstract, International Symposium on Abnormal Haemoglobins and Thalassaemias, Istanbul, Turkey, page 68, 1974. 2. Giardina, B., Brunori, M., Antonini, E., and Tentori, L.: Biochim. Biophys. Acta, 534:1, 1978. Hb J-Daloa beta57(E1)Asn->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated by IEF; Hb X moves faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; fingerprinting; amino acid analysis; CNBr DNA ANALYSES Not reported; presumed mutation AAC->GAC at codon 57 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a mother and son of the Bete tribe living on the Ivory Coast OTHER INFORMATION Quantity in the heterozygote 37% REFERENCES 1. Boissel, J.P., Wajcman, H., Labie, D., Fabritius, H., and Cabannes, R.: Hemoglobin, 6:433, 1982. Hb Dhofar beta58(E2)Pro->Arg ALSO KNOWN AS Yukuhashi CONTACT External HEMATOLOGY Mildly anemic with microcytosis and hypochromia; reticulocytosis (see below) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X occupies the position of Hb S) but not at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES A CCT->CGT mutation at codon 58 (Ref. 3) FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in Qara tribesmen living in Southern Arabia OTHER INFORMATION Quantity in the heterozygote is a low 15%; a beta+-thalassemic mutation [codon 29 (C->T) or IVS-I, -3 (C->T)] is present on the same chromosome; this thalassemia splicing mutation is responsible for the low level of Hb Dhofar REFERENCES 1. Marengo-Rowe, A.J., Lorkin, P.A., Gallo, E., and Lehmann, H.: Biochim. Biophys. Acta, 168:58, 1968. 2. Yanase, T., Hanada, M., Seita, M., Ohya, I., Ohta, Y., Imamura, T., Fujimura, T., Kawasaki, K., and Yamaoka, K.: Jpn. J. Hum. Genet., 13:40, 1968. 3. Williamson, D., Brown, K.P., Langdown, J.V., and Baglin, T.P.: Br. J. Haematol., 90:229, 1995. Hb I-High Wycombe beta59(E3)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is fast moving CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->GAG at codon 59 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in an English family and in a Australian family of German and Scottish descent OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Boulton, F.E., Huntsman, R.G., Lehmann, H., Lorkin, P., and Romero Herrera, A.E.: Br. J. Haematol., 20:671, 1971. 2. Wilkinson, T., Como, P., Brock, P., Kronenburg, H., Trent, R.J.A., and Brennan, S.O.: Hemoglobin, 11:51, 1987. Hb J-Kaohsiung beta59(E3)Lys->Thr ALSO KNOWN AS J-Honolulu CONTACT External HEMATOLOGY Not reported ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X is fast moving) but not at acidic pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; CNBr; carboxypeptidase B digestion for C-terminal determination DNA ANALYSES Not reported; presumed mutation AAG->ACG at codon 59 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a few Chinese families OTHER INFORMATION Quantity in the heterozygote 47% REFERENCES 1. Blackwell, R.Q., Liu, C-S., and Shih, T-B.: Biochim. Biophys. Acta, 229:343, 1971. 2. Shih, T-B.: Vox Sang., 22:469, 1972. Hb J-Lome beta59(E3)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate by standard techniques at alkaline pH and by IEF; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; CNBr; sequence by sequenator DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT at codon 59 FUNCTION STUDIES Normal STABILITY About normal OCCURRENCE Found in a family living in Lome, Togo OTHER INFORMATION Quantity in heterozygotes ~50%; also found in association with HPFH REFERENCES 1. Wajcman, H., Amegnizin, K.P.E., Belkhodja, O., and Labie, D.: FEBS Lett., 84: 372, 1977. 2. Amegnizin, K.P.E., Pagnier, J., Wajcman, H., Lapoumeroulie, C., and Labie, D.: Hemoglobin, 3:87, 1979. 3. Prior, J.F., Raven, J.L., Wilson, J.B., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 13:79, 1989. Hb Yatsushiro beta60(E4)Val->Leu CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves slower than Hb A CHROMATOGRAPHY Hb X elutes after Hb A on a CM-cellulose column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->CTG at codon 60 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Japanese individual OTHER INFORMATION Quantity in the heterozygote 45%; the electrophoretic and chromatographic separation of Hb X and Hb A is surprising; reevaluation of this variant is desirable; perhaps there is an additional amino acid replacement that was overlooked REFERENCES 1. Kagimoto, T., Morino, Y., and Kishimoto, S.: Biochim. Biophys. Acta, 532:195, 1978. Hb Collingwood beta60(E4)Val->Ala CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A observed at alkaline pH; no separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GCG at codon 60 FUNCTION STUDIES Normal oxygen affinity STABILITY Unstable OCCURRENCE Found in Greek male OTHER INFORMATION Quantity in the heterozygote 41% REFERENCES 1. Williamson, D., Brennan, S.O., Muir, H., and Carrell, R.W.: Hemoglobin, 7:511, 1983. Hb Cagliari beta60(E4)Val->Glu CONTACT Internal HEMATOLOGY Hemolytic anemia; microcytosis; hypochromia; thalassemia intermedia ELECTROPHORESIS No abnormal Hb was detected CHROMATOGRAPHY No abnormal Hb was detected STRUCTURE STUDIES Not possible; identification was by DNA analysis DNA ANALYSES A GTG->GAG mutation at codon 60 FUNCTION STUDIES Not possible STABILITY Highly unstable OCCURRENCE Found in an Italian child; no abnormalities in the parents OTHER INFORMATION The variant is highly unstable and is rapidly broken down resulting in a high Hb F level and reduced beta/alpha in vitro chain synthesis ratio; splenectomy improved the condition considerably REFERENCES 1. Podda, A., Galanello, R., Maccioni, L., Melis, M.A., Rosatelli, C., Perseu, L., and Cao, A.: Blood, 77:371, 1991. Hb N-Seattle beta61(E5)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate readily at alkaline pH (Hb X moves faster than Hb A) but not at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; leucine amino peptidase; Edman degradation DNA ANALYSES Not reported; presumed mutation AAG->GAG at codon 61 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Black male who was a blood donor OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Jones, R.T., Brimhall, B., Huehns, E.R., and Motulsky, A.G.: Biochim. Biophys. Acta, 154:278, 1968. Hb Hikari beta61(E5)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X has a mobility like Hb J CHROMATOGRAPHY Hb X and Hb A can be separated by different types of cation or anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; pronase digestion DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT at codon 61 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a few Japanese families OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Shibata, S., Miyaji, T., Iuchi, I., Ueda, S., and Takeda, I.: Clin. Chim. Acta, 10: 101, 1964. 2. Nakatsuji, T., Miwa, S., Hattori, Y., Ohba, Y., Miyaji, T., Miyata, H., Shinohara, T., and Matsui, Y.: Hemoglobin, 5:487, 1981. Hb Bologna beta61(E5)Lys->Met CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ATG at codon 61 FUNCTION STUDIES Decreased oxygen affinity; normal cooperativity and Bohr effect STABILITY Normal OCCURRENCE Found in a few members of a North Italian family OTHER INFORMATION Quantity in heterozygotes 47-48.5%; found in association with betao-thal REFERENCES 1. Marinucci, M., Giuliani, A., Maffi, D., Massa, A., Giampaolo, A., Mavilio, F., Zannotti, M., and Tentori, L.: Biochim. Biophys. Acta, 668:209, 1981. Hb Duarte beta62(E6)Ala->Pro CONTACT External HEMATOLOGY Near normal in the heterozygote; the proband with Hb X-beta-thal had mild hemolytic anemia, hypochromia, microcytosis, reticulocytosis ELECTROPHORESIS No separation reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; Dansyl-Edman degradation DNA ANALYSES Not reported; presumed mutation GCT->CCT at codon 62 FUNCTION STUDIES Increased oxygen affinity; normal cooperativity STABILITY Unstable OCCURRENCE Found in a father and son of German ancestry living in Duarte, California, USA OTHER INFORMATION Found with beta-thal REFERENCES 1. Beutler, E., Lang, A., and Lehmann, H.: Blood, 43:527, 1974. Hb Zurich beta63(E7)His->Arg CONTACT External; surface crevice; "distal histidine" HEMATOLOGY Normal in the heterozygote; certain oxidative drugs precipitate hemolytic episodes with inclusion bodies ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves slightly faster than Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; chymotryptic digestion DNA ANALYSES Not reported; presumed mutation CAT->CGT at codon 63 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Mildly unstable OCCURRENCE Found in families from Switzerland and from the USA OTHER INFORMATION Quantity in the heterozygote 22-35%; stability of the variant is influenced by oxidative drugs REFERENCES 1. Hitzig, W.H., Frick, P.G., Betke, K., and Huisman, T.H.J.: Helv. Paediatr. Acta, 15:399, 1960. 2. Muller, C.J. and Kingma, S.: Biochim. Biophys. Acta, 40:595, 1961. 3. Frick, P.G., Hitzig, W.H., and Betke, K.: Blood, 20:261, 1962. Hb M-Saskatoon beta63(E7)His->Tyr ALSO KNOWN AS M-Emory; M-Kurume; M-Hida; M-Radom; M-Arthus; M-Chicago; Leipzig; Horlein-Weber; Novi Sad; M-Erlangen CONTACT External; surface crevice; "distal histidine" HEMATOLOGY Compensated hemolytic anemia in the heterozygote; ferriHb; cyanosis ELECTROPHORESIS Hb X and Hb A have about the same mobility at alkaline pH; when converted to metHb, Hb X moves faster than Hb A at pH 7.0 CHROMATOGRAPHY Hb X was isolated on Amberlite IRC-50 (elutes after Hb A); DEAE-Sephadex (incompletely separated from Hb A2) STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAT->TAT at codon 63 FUNCTION STUDIES Oxygen affinity reported as normal or decreased by different investigators STABILITY Unstable; dissociates into dimers at pH 10.1 OCCURRENCE Found in families from Georgia, USA, Japan, England, Denmark, Norway, Yugoslavia, Canada, Poland, etc. OTHER INFORMATION The variant often occurs as a de novo mutation; quantity in heterozygotes 24-27%; absorption maxima 490-598 nm, which is specific for this variant REFERENCES 1. Gerald, P.S. and Efron, M.L.: Proc. Natl. Acad. Sci. USA, 47:1758, 1961. 2. Shibata, S., Miyaji, T., Iuchi, I., and Ueda, S.: Acta Haematol. Jpn., 24:486, 1961. 3. Josephson, A.M., Weinstein, H.G., Yakulis, V.J., Singer, L., and Heller, P.: J. Lab. Clin. Med., 59:918, 1962. Hb Bicetre beta63(E7)His->Pro CONTACT External; surface crevice; "distal histidine" HEMATOLOGY Severe hemolytic anemia with Heinz bodies ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; detection of the variant based on stability CHROMATOGRAPHY No separation by cation or anion exchange chromatography; the betaX and betaA chains separate by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography or reversed phase HPLC; amino acid analysis; sequence by sequenator DNA ANALYSES Not reported; presumed mutation CAT->CCT at codon 63 FUNCTION STUDIES Normal STABILITY Unstable; auto-oxidizing OCCURRENCE Found in a French male and an American male; not found in either parents or siblings OTHER INFORMATION Quantity in the heterozygotes 20-25% REFERENCES 1. Wajcman, H., Krishnamoorthy, R., Gacon, G., Elion, J., Allard, C., and Labie, D.: J. Mol. Med., 1:187, 1976. 2. Miller, D.R., Wilson, J.B., Kutlar, A., and Huisman, T.H.J.: Am. J. Hematol., 21: 209, 1986. Hb J-Calabria beta64(E8)Gly->Asp ALSO KNOWN AS J-Bari; J-Cosenza CONTACT Internal HEMATOLOGY Normal in the heterozygote; Heinz bodies produced by brilliant cresyl blue ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGC->GAC at codon 64 FUNCTION STUDIES Increased oxygen affinity; normal cooperativity and Bohr effect STABILITY Mildly unstable OCCURRENCE Found in members of a French family and in a Chinese male OTHER INFORMATION Quantity in heterozygotes 38%; found in combination with beta-thal REFERENCES 1. Blouquit, Y., Thillet, J., Beuzard, Y., Vernant, J.P., and Dreyfus, B.: Biochim. Biophys. Acta, 492:426, 1977. 2. Chen, S., Yang, K., Jia, P., Liang, C., Long, G., Tang, Z., Huang, L., Su, R., Yu, C., and Liang, X.: Acta Acad. Med. Sin., 4:6, 1982. Hb J-Sicilia beta65(E9)Lys->Asn CONTACT External HEMATOLOGY Slight anemia in the heterozygote; anemia likely unrelated to the presence of the variant ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase B DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT at codon 65 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Sicilian female OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Ricco, G., Pich, P.G., Mazza, U., Rossi, G., Ajmar, F., Arese, P., and Gallo, E.: FEBS Lett., 39:200, 1974. Hb J-Cairo beta65(E9)Lys->Gln CONTACT External HEMATOLOGY Slight hypochromic microcytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X is faster than Hb A) but not at acidic pH; excellent separation by IEF CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->CAG at codon 65 FUNCTION STUDIES Decreased oxygen affinity and cooperativity; normal Bohr effect STABILITY Normal; increased auto-oxidation OCCURRENCE Found in an Egyptian female and her father OTHER INFORMATION Quantity in heterozygotes 40-45% REFERENCES 1. Garel, M.C., Hassan, W., Coquelet, M.T., Goossens, M., and Rosa, J.: Biochim. Biophys. Acta, 420:97, 1976. Hb J-Antakya beta65(E9)Lys->Met NOTE: This variant was erroneously identified as beta127(H5)Gln->Glu (Altay, C., Altinoz, N., Wilson, J.B., Bolch, K.C., and Huisman, T.H.J.: Biochim. Biophys. Acta, 434:1, 1976); a variant with this substitution has been observed in a Spanish family and is known as Hb Complutense CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X is faster than Hb A); no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->ATG at codon 65 FUNCTION STUDIES Not observed STABILITY Normal OCCURRENCE Found in members of a family from Southern Turkey OTHER INFORMATION Quantity in the heterozygote 41% REFERENCES 1. Huisman, T.H.J., Wilson, J.B., Kutlar, A., Yang, K-G., Chen, S-S., Webber, B.B., Altay, C., and Villegas Martinez, A.: Biochim. Biophys. Acta, 871:229, 1986. Hb I-Toulouse beta66(E10)Lys->Glu CONTACT Heme contact HEMATOLOGY Mild chronic hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves considerably faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; Edman degradation DNA ANALYSES Not reported; presumed mutation AAA->GAA at codon 66 FUNCTION STUDIES Normal STABILITY Unstable; ferriHb OCCURRENCE Found in a French male, a Nicaraguan female in association with Hb S, and in Solomon Islanders in association with alpha-thal OTHER INFORMATION Quantity in heterozygotes 33-40% (lowest value in the subjects with alpha-thal); tendency to form metHb REFERENCES 1. Rosa, J., Labie, D., Wajcman, H., Boigne, J.M., Cabannes, R., Bierme, R., and Ruffie, J.: Nature, 223:190, 1969. 2. Labie, D., Rosa, J., Belkhodja, O., and Bierme, R.: Biochim. Biophys. Acta, 236:201, 1971. 3. Hendy, J.G. and Cauchi, M.N.: Hemoglobin, 18:227, 1994. Hb Chico beta66(E10)Lys->Thr CONTACT Heme contact HEMATOLOGY Mild anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X has the mobility of Hb J) but not at acidic pH CHROMATOGRAPHY Incomplete separation of Hb X and Hb A by cation exchange HPLC; good separation by DEAE-Sephadex chromatography; betaA, betaX, and alpha chains separate in reversed phase HPLC; elution in the order listed STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAA->ACA at codon 66 FUNCTION STUDIES Decreased oxygen affinity; normal cooperativity STABILITY Slightly unstable OCCURRENCE Found in a family living in Chico, California, USA OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Shih, D.T-B., Jones, R.T., Shih, M.F-C., Jones, M.B., Koler, R.D., and Howard, J.: Hemoglobin, 11:453, 1987. Hb M-Milwaukee-I beta67(E11)Val->Glu CONTACT Heme contact HEMATOLOGY Ferrihemoglobinemia in the heterozygote ELECTROPHORESIS Variable patterns because of metHb formation; cyanmetHb X separates from Hb A by alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X can be isolated by Amberlite CG-50 chromatography; Hb X elutes after Hb A STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GAG at codon 67 FUNCTION STUDIES Decreased oxygen affinity and cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in quite a few families in different populations OTHER INFORMATION Quantity in the heterozygote 26-40%; absorption maxima 500 and 623 nm are specific for this mutation REFERENCES 1. Pisciotta, A.V., Ebbe, S.N., and Hinz, J.E.: J. Lab. Clin. Med., 54:73, 1969. 2. Gerald, P.S. and Efron, M.L.: Proc. Natl. Acad. Sci. USA, 47:1758, 1961. 3. Hayashi, A., Suzuki, T., Imai, K., Morimoto, H., and Watari, H.: Biochim. Bio-phys. Acta, 194:6, 1969. 4. Udem, L., Ranney, H.M., Bunn, H.F., and Pisciotta, A.: J. Mol. Biol., 48:489, 1970. Hb Bristol beta67(E11)Val->Asp NOTE: A recent study by Rees et al (Ref. 3) concerns the analysis of the Hb Bristol abnormality in the original family and in two Japanese heterozygotes. All three have a GTG->ATG mutation by sequencing analysis as in Hb Alesha (beta67, Val->Met). Posttranslational modifications are believed to change some of the properties of the abnormal Hb such as an increased mobility; this could contribute to an an inaccurate identification. The formation of a Hb fraction in the Hb Alesha heterozygote with an Asp->Met replacement has not been reported CONTACT Heme contact HEMATOLOGY Congenital non-spherocytic hemolytic anemia with Heinz body formation; reticulocytosis ELECTROPHORESIS Moves with Hb A at alkaline pH; no other reports available CHROMATOGRAPHY Not reported STRUCTURE STUDIES pCMB; tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported (see Other Information) FUNCTION STUDIES Decreased oxygen affinity, cooperativity, and Bohr effect STABILITY Unstable OCCURRENCE Found in an English male and not his parents; Ref. 1 describes the first clinical data OTHER INFORMATION Quantity in the heterozygote 36%. The normally occurring codon GTG cannot be mutated through a single base change to GAT (Asp) or GAC (Asp). There are two possibilities: a) The Hb is misdiagnosed and is in fact Hb M-Milwaukee-I (GTG->GAG; Val->Glu) or b) the original codon in this subject was GTT or GTC; the two can be mutated to GAT (Asp) or GAC (Asp); further study of this patient is recommended REFERENCES 1. Cathie, I.A.B.: Great Ormond St. J., 2:43, 1952. 2. Steadman, J.H., Yates, A., and Huehns, E.R.: Br. J. Haematol., 18:435, 1970. 3. Rees, D.C., Rochette, J., Green, B., Schofield, C.J., Ohba, Y., and Clegg, J.B.: Blood, 88:6a (Suppl. 1), 1995. Hb Alesha beta67(E11)Val->Met CONTACT Heme contact HEMATOLOGY Inclusion body hemolytic anemia, reticulocytosis; no cyanosis; Heinz bodies; no methemoglobinemia ELECTROPHORESIS No separation by standard procedures CHROMATOGRAPHY Partial separation of Hb X and Hb A by cation exchange HPLC; no separation of betaX and betaA by reversed phase HPLC STRUCTURE STUDIES Not reported; identification through DNA analysis DNA ANALYSES A GTG->ATG mutation at codon 67 FUNCTION STUDIES Slightly increased auto-oxidation STABILITY Unstable OCCURRENCE Found in a young Russian boy but not in his parents OTHER INFORMATION Quantity in the heterozygote 18-25 REFERENCES 1. Molchanova, T.P., Postnikov, Yu.V., Pobedimskaya, D.D., Smetanina, N.S., Moschan, A.A., Kazanetz, E.G., Tokarev, Yu.N., and Huisman, T.H.J.: Hemoglobin, 17:217, 1993. Hb Sydney beta67(E11)Val->Ala CONTACT Heme contact HEMATOLOGY Inclusion body hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves as a broad band behind Hb A at alkaline pH CHROMATOGRAPHY Not studied STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GCG at codon 67 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a German and an English family OTHER INFORMATION Quantity in the heterozygote 40%; an additional structural change observed at beta141 leucine->hydroxyleucine (see also Hb Manukau; Hb Atlanta) REFERENCES 1. Carrell, R.W., Lehmann, H., Lorkin, P.A., Raik, E., and Hunter, E.: Nature, 215: 626, 1967. 2. Casey, R., Lang, A., Lehmann, H., and Shinton, N.K.: Br. J. Haematol., 33:143, 1976. Hb Manukau beta67(E11)Val->Gly CONTACT Heme contact HEMATOLOGY Moderate monochromic normocytic anemia; no cyanosis; no Heinz bodies ELECTROPHORESIS No abnormal Hb detected by standard techniques, including IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; betaT-9 and betaT-8,9 were abnormal (Val-> Gly); peptide betaT-14 was also abnormal (beta141 Leu oxidized to beta141 hydroxyleucine); see also Hb Atlanta (beta75 Leu->Pro) DNA ANALYSES A GTG->GGG mutation at codon 67 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a father and two sons of a Niuean/Maori family from New Zealand OTHER INFORMATION Father mildly affected; he is an alpha-thal-2 homozygote (-alpha/alphaalpha); the two sons are more severely affected; both have the -alpha/alphaalphaalpha genic arrangement REFERENCES 1. Fay, K.C., Brennan, S.O., Costello, J.M., Potter, H.C., Williamson, D.A., Trent, R.J., Ockleford, P.A., and Boswell, D.R.: Br. J. Haematol., 85:352, 1993. Hb Mizuho beta68(E12)Leu->Pro CONTACT Internal HEMATOLOGY Severe hemolytic anemia in the heterozygote ELECTROPHORESIS No abnormal Hb detected by routine procedures CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES A CTC->CCC mutation at codon 68 (Refs. 3 and 4) FUNCTION STUDIES Not determined STABILITY Unstable OCCURRENCE Found in a Japanese girl, an Italian girl, a Caucasian boy from Kentucky, and a Dutch boy; all are de novo mutations OTHER INFORMATION Clinical improvement after splenectomy REFERENCES 1. Ohba, Y., Miyaji, T., Matsuoka, M., Sugiyama, K., Suzuki, T., and Sugiura, T.: Hemoglobin, 1:467, 1977. 2. Labotka, R.J., Vida, L.N., and Honig, G.R.: Hemoglobin, 14:129, 1990. 3. Keeling, M.M., Bertolone, S.J., Baysal, E., Gu, Y-C., Cepreganova, B., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 15:477, 1991. 4. Harthoorn-Lasthuizen, E.J., Nabben, F.A.E., Kazanetz, E.G., Gu, L-H., Mol-chanova, T.P., and Huisman, T.H.J.: Hemoglobin, 19:203, 1995. Hb Brisbane beta68(E12)Leu->His ALSO KNOWN AS Great Lakes CONTACT Internal HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures; the abnormal Hb was detected by stability tests CHROMATOGRAPHY The betaX and betaA chains could be separated by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; chymotrypsin; Dansyl-Edman degradation DNA ANALYSES Not reported; presumed mutation CTC->CAC at codon 68 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect and 2,3-DPG binding STABILITY Decreased stability OCCURRENCE Found in a mother and son living in New Zealand and a 29-year-old Caucasian female in the USA OTHER INFORMATION None REFERENCES 1. Carrell, R.W.: Hemoglobin, 4:427, 1980. 2. Brennan, S.O., Wells, R.M., Smith, H., and Carrell, R.W.: Hemoglobin, 5:325, 1981. 3. Rahbar, S., Winkler, K., Louis, J., Rea, C., Blume, K., and Beutler, E.: Blood, 58: 813, 1981. 4. Williamson, D., Brennan, S.O., and Carrell, R.W.: Hemoglobin, 7:473, 1983. Hb Rambam beta69(E13)Gly->Asp ALSO KNOWN AS J-Cambridge CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES ryptic digestion; separation of peptides by fingerprinting; chymotryptic digestion; amino acid analysis; leucine amino peptidase DNA ANALYSES Not reported; presumed mutation GGT->GAT at codon 69 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Bedouin family from Israel and an English family OTHER INFORMATION Quantity in the heterozygote not reported REFERENCES 1. Salomon, H., Tatarski, I., Dance, N., Huehns, E.R., and Shooter, E.M.: Israel J. Med. Sci., 1:836, 1965. 2. Sick, K., Beale, D., Irvine, D., Lehmann, H., Goodall, P.T., and MacDougall, S.: Biochim. Biophys. Acta, 140:231, 1967. Hb City of Hope beta69(E13)Gly->Ser CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separations obtained CHROMATOGRAPHY No separation reported; the betaX chain elutes between betaA and alpha by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing; FAB mass spectrometry DNA ANALYSES A GGT->AGT mutation at codon 69 (Refs. 2 and 3) FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a Caucasian family from California, an Italian family from Naples, a Turkish family, and a Jewish family from Augusta, Georgia OTHER INFORMATION Quantity in the heterozygote ~50% (Ref. 2); occurred in combination with betao-thal->thalassemia intermedia REFERENCES 1. Rahbar, S., Asmerom, Y., and Blume, K.G.: Hemoglobin, 8:333, 1984. 2. Kutlar, A., Kutlar, F., Aksoy, M., Gurgey, A., Altay, C., Wilson, J.B., Diaz-Chico, J.C., Hu, H., and Huisman, T.H.J.: Hemoglobin, 13:7,1989. 3. De Angioletti, M., Maglione, G., Ferranti, P., de Bonis, C., Lacerra, G., Scarallo, A., Pagano, L., Fioretti, G., Cutolo, R., Malorni, A., Pucci, P., and Carestia, C.: Hemoglobin, 16:27, 1992. Hb Kenitra beta69(E13)Gly->Arg CONTACT External HEMATOLOGY Probably normal; the proband had an additional alpha-thal, resulting in microcytosis, hypochromia ELECTROPHORESIS Hb X slowly separates from Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGT->CGT at codon 69 FUNCTION STUDIES Not determined STABILITY Normal OCCURRENCE Found in a Moroccan family OTHER INFORMATION Quantity in the heterozygote ~55% (densitometry) REFERENCES 1. Delanoe-Garin, J., Arous, N., Blouquit, Y., Hafsia, R., Bardakdjian, J., Lacombe, C., Rosa, J., and Galacteros, F.: Hemoglobin, 9:1, 1985. Hb Seattle beta70(E14)Ala->Asp CONTACT Heme contact HEMATOLOGY Mild chronic hemolytic anemia; Heinz bodies after incubation with brilliant cresyl blue ELECTROPHORESIS Hb X and Hb A separate at alkaline pH and by IEF; Hb X moves like Hb J; no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by both cation and anion exchange HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 70 FUNCTION STUDIES Decreased oxygen affinity, cooperativity, and Bohr effect STABILITY Unstable OCCURRENCE Found in a Caucasian family (USA) and in an Ukrainian family OTHER INFORMATION Variant was wrongly identified as beta76(E20)Ala->Glu (Ref. 1); corrected (Ref. 3); quantity in the heterozygote 26-37% REFERENCES 1. Huehns, E.R., Hecht, F., Yoshida, A., Stamatoyannopoulos, G., Hartman, J., and Motulusky, A.G.: Blood, 36:209, 1970. 2. Stamatoyannopoulos, G., Parer, J.T., and Finch, C.A.: N. Engl. J. Med., 281:915, 1969. 3. Anderson, N.L., Perutz, M.F., and Stamatoyannopoulos, G.: Nature, 243:274, 1973. 4. Kurachi, S., Hermodson, M., Hornung, S., and Stamatoyannopoulos, G.: Nature, 243:275, 1973. 5. Chow, E.Y., Haley, L.P., Krikler, S.H., and Wadsworth, L.D.: Hemoglobin, 18: 231, 1994. Hb Christchurch beta71(E15)Phe->Ser CONTACT Heme contact HEMATOLOGY Heinz body hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves with Hb A on various media at various pH values CHROMATOGRAPHY Not reported STRUCTURE STUDIES 14C-labeled hydrolysate; fingerprinting; chymotrypsin; amino acid analysis; autoradiographs DNA ANALYSES Not reported; presumed mutation TTT->TCT at codon 71 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in an 18-year-old female living in Australia OTHER INFORMATION Quantity in the heterozygote about 22% REFERENCES 1. Carrell, R.W. and Owen, M.C.: Biochim. Biophys. Acta, 236:507, 1971. Hb Headington beta72(E16)Ser->Arg CONTACT External HEMATOLOGY Mild erythrocytosis in the proband who also had a (deltabeta)o-thal ELECTROPHORESIS Hb X occupies the position of Hb S at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported; identification was by DNA analysis DNA ANALYSES An AGT->AGA mutation at codon 72 FUNCTION STUDIES Increase in oxygen affinity; slight decrease in cooperativity; Bohr effect normal STABILITY Normal OCCURRENCE Found in an Asian Indian family OTHER INFORMATION Occurred in combination with a (deltabeta)o-thal REFERENCES 1. Rochette, J., Barnetson, R., Kiger, L., Kister, J., Littlewood, T.J., Webster, R., Poyart, C., and Thein, S.L.: Br. J. Haematol., 86:118, 1994. Hb Vancouver beta73(E17)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slightly ahead of Hb S; no separation at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; chymotrypsin DNA ANALYSES Not reported; presumed mutation GAT->TAT at codon 73 FUNCTION STUDIES Decreased oxygen affinity; normal Bohr effect, cooperativity, and 2,3-DPG effect STABILITY Normal OCCURRENCE Found in a family from Canton, China living in Canada OTHER INFORMATION Found in association with beta-thal; quantity in the heterozygote 40% REFERENCES 1. Jones, R.T., Brimhall, B., Pootrakul, S., and Gray, G.: J. Mol. Evol., 9:37, 1976. 2. Gray, G.R. and Marion, R.B.: Hemoglobin, 2:143, 1978. Hb Korle-Bu beta73(E17)Asp->Asn ALSO KNOWN AS G-Accra CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X occupies the position of Hb S; no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography; the betaX and betaA chains separate by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; chymotrypsin digestion; carboxypeptidase; sequencing; mass spectrometry DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 73 FUNCTION STUDIES Decreased oxygen affinity; normal Bohr, cooperativity, and 2,3-DPG effects STABILITY Normal OCCURRENCE Found in Black families from Ghana, the Ivory Coast, Costa Rica, Mexico, etc. OTHER INFORMATION Found in combination with Hb S and with Hb C; homozygote is clinically normal REFERENCES 1. Lehmann, H., Beale, D., and Boi-Doku, F.S.: Nature, 203:363, 1964. 2. Konotey-Ahulu, F.I.D., Gallo, E., Lehmann, H., and Ringelhann, B.: J. Med. Genet., 5:107, 1968. 3. Nagel, R.L., Lin, M.J., Witkowska, H.E., Fabry, M.E., Bestak, M., and Hirsch, R.E.: Blood, 82:1907, 1993. Hb Mobile beta73(E17)Asp->Val CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X is slightly faster than Hb S); no separation at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->GTT at codon 73 FUNCTION STUDIES Decreased oxygen affinity; normal Bohr, cooperativity, and 2,3-DPG effect STABILITY Not reported but presumably normal OCCURRENCE Found in three Black families living in Alabama OTHER INFORMATION Quantity in the heterozygote 42%; found in combination with Hb S REFERENCES 1. Schneider, R.G., Hosty, T.S., Tomlin, G., Atkins, R., Brimhall, B., and Jones, R.T.: Biochem. Genet., 13:411, 1975. 2. Schneider, R.G., Smith, W.B., Zusman, J., King, T.D., Jones, R.T., and Brimhall, B.: Blood, 52:118 (Suppl. 1), 1978. 3. Jones, R.T. and Koler, R.D.: Abstract, 16th International Congress of Hematol-ogy, Kyoto, Japan, page 48, 1976. 4. Jones, R.T., Brimhall, B., Pootrakul, S., and Gray, G.: J. Mol. Evol., 9:37, 1976. Hb Tilburg beta73(E17)Asp->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slower than Hb A but slightly faster than Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; sequencing; mild acid hydrolysis of betaT-9 DNA ANALYSES Not reported; presumed mutation GAT->GGT at codon 73 FUNCTION STUDIES Decreased oxygen affinity; normal Bohr effect STABILITY Stable OCCURRENCE Found in a Dutch family OTHER INFORMATION Quantity in the heterozygote 42% REFERENCES 1. Bernini, L.F. and Giordano, P.C.: Biochim. Biophys. Acta, 957:281, 1988. Hb Bushwick beta74(E18)Gly->Val CONTACT Internal HEMATOLOGY Chronic hemolytic anemia with episodes of severe hemolysis associated with drug administration and fever; reticulocytosis; homozygote has a severe hemolytic disease ELECTROPHORESIS No good separation obtained; smears CHROMATOGRAPHY No adequate separation obtained; betaX separates from betaA and alpha by reversed phase HPLC (elution order: betaA, alpha, betaX) STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GGC->GTC mutation at codon 74 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in members of an Italian-American family and in a Yugoslavian family; the homozygote is a Pakistani female OTHER INFORMATION Quantity in the heterozygote 35-40% (betaX/betaA separation by reversed phase HPLC) REFERENCES 1. Rieder, R.F., Wolf, D.J., Clegg, J.B., and Lee, S.L.: Nature, 254:725, 1975. 2. Efremov, G.D., Jankovic, L., Juricic, D., Stojancov, A., Wilson, J.B., Webber, B.B., Kutlar, F., Kutlar, A., Hu, H., and Huisman, T.H.J.: Hemoglobin, 11:537, 1987. 3. Srivastava, P., Kaeda, J.S., Roper, D., Vulliamy, T.J., Buckley, M., and Luzzatto, L.: Blood, 86:1977, 1995. Hb Shepherds Bush beta74(E18)Gly->Asp CONTACT Internal HEMATOLOGY Heinz body hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb J CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; thermolysin DNA ANALYSES Not reported; presumed mutation GGC->GAC at codon 74 FUNCTION STUDIES Increased oxygen affinity; decreased 2,3-DPG effect STABILITY Unstable OCCURRENCE Found in a South African female of British origin; a father and three daughters of one Sicilian family, and two siblings of another Sicilian family OTHER INFORMATION Quantity in the heterozygote about 24% REFERENCES 1. White, J.M., Brain, M.C., Lorkin, P.A., Lehmann, H., and Smith, M.: Nature, 225: 939, 1970. 2. May, A. and Huehns, E.R.: Br. J. Haematol., 22:599, 1972. 3. Sansone, G., Sciarratta, G.V., Genova, R., Darbre, P.D., and Lehmann, H.: Acta Haematol., 57:102, 1977. 4. Schiliro, G., Musumeci, S., Russo, A., Russo, G., Marinucci, M., Giampaola, A., Cianetti, L., and Tentori, L.: Hemoglobin, 5:493, 1981. Hb Aalborg beta74(E18)Gly->Arg CONTACT Internal HEMATOLOGY Mild anemia in the heterozygote; Heinz bodies ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X has a mobility between that of Hb F and Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; peptides were characterized by FAB mass spectrometry DNA ANALYSES Not reported; presumed mutation GGC->CGC at codon 74 FUNCTION STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in a 7-year-old girl and her father OTHER INFORMATION Quantity in the heterozygote ~21% REFERENCES 1. Williamson, D., Nutkins, J., Rosthoj, S., Brennan, S.O., Williams, D.H., and Carrell, R.W.: Hemoglobin, 14:137, 1990. Hb Atlanta beta75(E19)Leu->Pro CONTACT Internal HEMATOLOGY Mild hemolytic anemia in the heterozygote with Heinz body formation; reticulocytosis ELECTROPHORESIS No separation with standard procedures; good separation with IEF CHROMATOGRAPHY No separation by cation or anion exchange HPLC; betaX and betaA readily separate by reversed phase HPLC STRUCTURE STUDIES pCMB precipitation; tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; Edman-Dansyl degradation DNA ANALYSES A CTG->CCG mutation at codon 75 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in several members of a Caucasian family living in Atlanta, Georgia, USA; in a patient from New Zealand, and in a large Dutch family (unpublished) OTHER INFORMATION Splenectomy improves anemia; quantity in the heterozygote 33%; a leucine->hydroxyleucine change occurred, indirectly caused by the Leu->Pro replacement at codon 75 REFERENCES 1. Hubbard, M., Winton, E.F., Lindeman, J.G., Dessauer, P.L., Wilson, J.B., Wrightstone, R.N., and Huisman, T.H.J.: Biochim. Biophys. Acta, 386:538, 1975. 2. Brennan, S.O., Williamson, D., Symmans, W.A., and Carrell, R.W.: Hemoglobin, 7:303, 1983. 3. Brennan, S.O., Williamson, D., Symmans, W.A., and Carrell, R.W.: Hemoglobin, 10:225, 1986. 4. Brennan, S.O., Shaw, J.G., George, P.M., and Huisman, T.H.J.: Hemoglobin, 17: 1, 1993. Hb Pasadena beta75(E19)Leu->Arg CONTACT Internal HEMATOLOGY Compensated hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb S and Hb F; no separation at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG at codon 75 FUNCTION STUDIES Decreased oxygen affinity and cooperativity STABILITY Unstable OCCURRENCE Found in a 27-year-old male of Southern French ancestry but not in his parents OTHER INFORMATION Quantity in the heterozygote 31-32% REFERENCES 1. Johnson, C.S., Moyes, D., Schroeder, W.A., Shelton, J.B., Shelton, J.R., and Beutler, E.: Biochim. Biophys. Acta, 623:360, 1980. Hb J-Chicago beta76(E20)Ala->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; chymotrypsin DNA ANALYSES Not reported; presumed mutation GCT->GAT at codon 76 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 2-year-old Black male living in Chicago, Illinois, USA OTHER INFORMATION Quantity in the heterozygote 51.6% REFERENCES 1. Romain, P.L., Schwartz, A.D., Shamsuddin, M., Adams, J.G., III, Mason, R.G., Vida, L.N., and Honig, G.R.: Blood, 45:387, 1975. Hb Calais beta76(E20)Ala->Pro CONTACT External HEMATOLOGY Chronic anemia; patient also had severe Fe deficiencies ELECTROPHORESIS No separation by standard procedures; separation by IEF (Hb X focuses between Hb A and Hb A1) CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digest of AE-beta chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCT->CCT at codon 76 FUNCTION STUDIES Decreased oxygen affinity; increased metHb formation STABILITY Not reported OCCURRENCE Found in a 43-year-old French woman from Calais, France OTHER INFORMATION Quantity in the heterozygote ~40% REFERENCES 1. Wajcman, H., Kister, J., Marden, M., Bohn, B., Blouquit, Y., Descamps, J., Goudemand, M., Poyart, C., and Galacteros, F.: Biochim. Biophys. Acta, 1096:60, 1991. Hb J-Iran beta77(EF1)His->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is fast moving CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC or by fingerprinting; amino acid analysis; chymotrypsin; sequencing DNA ANALYSES Not reported; presumed mutation CAC->GAC at codon 77 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in an Iranian family and in a Turkish family OTHER INFORMATION Quantity in the heterozygote 43-47% REFERENCES 1. Rahbar, S., Beale, D., Isaacs, W.A., and Lehmann, H.: Br. Med. J., 1:674, 1967. 2. Arcasoy, A., Turhanoglu, I., Gozdasoglu, S., and Ogur, G.: Hemoglobin, 10:209, 1986. Hb Fukuyama beta77(EF1)His->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate by IEF; Hb X focuses with Hb A1c CHROMATOGRAPHY Hb X and Hb A separate by cation exchange HPLC; Hb X elutes ahead of Hb A together with Hb A1c; the betaX and betaA chains separate by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES A CAC->TAC mutation at codon 77 (Ref. 4) FUNCTION STUDIES Not reported STABILITY Slightly abnormal OCCURRENCE Found in a 64-year-old Japanese male, a Caucasian family in the United States; an Indonesian woman, and two unrelated Swedish women OTHER INFORMATION Quantity in the heterozygote 31-34% (a subject with an alpha-thal-1 heterozygosity) (Ref. 3); heterozygote with four alpha-globin genes has 47% Hb X REFERENCES 1. Hidaka, K., Iuchi, I., Miyake, K., Nakahara, H., and Iwakawa, G.: Hemoglobin, 12: 391, 1988. 2. Moo-Penn, W.F., Hine, T.K., Johnson, M.H., Jue, D.L., Piersma, H., Therrell, B., Jr., and Chu, A.: Hemoglobin, 15:97, 1991. 3. Smit, J.W., Deggeller, K., Tamminga, R.Y.J., Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 15:331, 1991. 4. Jeppsson, J-O. and Landin, B.: Hemoglobin, 17:303, 1993. Hb Quin-Hai beta78(EF2)Leu->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb F and Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTG->CGG at codon 78 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Chinese family OTHER INFORMATION Quantity in the heterozygote 21.7% (elution from cellulose acetate) REFERENCES 1. Jen, P.C., Chen, L.C., Chen, P.F., Wong, Y., Chen, L.F., Guo, Y.Y., Chang, F.Q., Chow, Y.C., and Chiu, Y.: Hemoglobin, 7:407, 1983. Hb G-Hsi-Tsou beta79(EF3)Asp->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb A and Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GGC at codon 79 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Chinese family from Hopei Province, PR China OTHER INFORMATION Quantity in the heterozygote 46% REFERENCES 1. Blackwell, R.Q., Shih, T-B., Wang, C-L., and Liu, C-S.: Biochim. Biophys. Acta, 257:49, 1972. Hb Tampa beta79(EF3)Asp->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote and the homozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb S and Hb F CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC, fingerprinting, and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->TAC at codon 79 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 6-year-old Caucasian male; both parents have the trait and the child is homozygous for Hb X OTHER INFORMATION Quantity in the heterozygote 33% REFERENCES 1. Johnson, M.H., Jue, D.L., Patchen, L.C., Hartwig, E.C., Schneider, M.J., and Moo-Penn, W.F.: Biochim. Biophys. Acta, 623:119, 1980. Hb Tigraye beta79(EF3)Asp->His CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X has a mobility like Hb S; at acidic pH Hb X is located between Hb S and Hb C CHROMATOGRAPHY Hb X elutes behind Hb C by cation exchange HPLC; the betaX chain elutes before the betaA chain on a reversed phase HPLC column STRUCTURE STUDIES Not reported; identification by DNA analysis only DNA ANALYSES A GAC->CAC mutation at codon 79 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a healthy Ethiopian male OTHER INFORMATION Quantity in the heterozygote 39.4% REFERENCES 1. Molchanova, T.P., Postnikov, Yu.V., Gu, L-H., Prior, J.F., Raven, J.L., Bennett, J.A., and Huisman, T.H.J.: Hemoglobin, 17:247, 1993. Hb Yaizu beta79(EF3)Asp->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Variant was detected as a slow-moving Hb by IEF CHROMATOGRAPHY Hb X and Hb A separate by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAC->AAC mutation at codon 79 FUNCTION STUDIES Not reported STABILITY Stable OCCURRENCE Found in a Japanese female OTHER INFORMATION Quantity in the heterozygote 41.4% REFERENCES 1. Harano, T., Harano, K., and Katsuki, T.: Hemoglobin, 19:21, 1995. Hb G-Szuhu beta80(EF4)Asn->Lys ALSO KNOWN AS Gifu CONTACT 2,3-DPG pocket HEMATOLOGY Normal in the heterozygote and presumably also in the homozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb S or slightly faster CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography; Hb X and Hb A also separate by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC or by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->AAA or AAG at codon 80 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a Chinese family from Taiwan; a Jewish family of Turkish extraction; in members of an English family; a Spanish family, and a Sicilian family OTHER INFORMATION Quantity in the heterozygote 36-40%; homozygote also suffered from abetalipoproteinemia; occurs together with beta-thal REFERENCES 1. Blackwell, R.Q., Yang, H.J., and Wang, C.C.: Biochim. Biophys. Acta, 188:59, 1969. 2. Kaufman, S., Leiba, H., Clejan, L., Wallis, K., Lorkin, P.A., and Lehmann, H.; Hum. Hered., 25:60, 1975. 3. Schiliro, G., Russo-Mancusso, G., Dibenedetto, S.P., Samperi, P., Di Cataldo, A., Ragusa, R., and Testa, R.: Hemoglobin, 15:431, 1991. Hb Baylor beta81(EF5)Leu->Arg CONTACT 2,3-DPG pocket HEMATOLOGY Hemolytic process present but with relatively high Hb and red cell values; Heinz bodies ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slightly faster than Hb S; at acidic pH Hb X moves between Hb A and Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; cation exchange chromatography; glycin-amidation; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTC->CGC at codon 81 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Unstable OCCURRENCE Found in a Caucasian male of Italian-Irish parentage OTHER INFORMATION Quantity in the heterozygote ~22% REFERENCES 1. Schneider, R.G., Hettig, R.A., Bilunos, M., and Brimhall, B.: Hemoglobin, 1:85, 1977. Hb La Roche-sur-Yon beta81(EF5)Leu->His (beta80 Asn is partially deaminated) CONTACT 2,3-DPG pocket HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS The presence of two abnormal Hb components were observed by IEF; one (15%) displayed a pI slightly above that of Hb A; the second (12%) focused with a lower pI than Hb F; globin chain electrophoresis in 6 M urea at pH 6.0 showed two abnormal beta chains and only one at pH 9.0 CHROMATOGRAPHY Not reported; the betaX and betaA chains can be separated by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; peptides were separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTC->CAC at codon 81 FUNCTION STUDIES Slightly increased oxygen affinity STABILITY Unstable OCCURRENCE Found in an 18-year-old female of Portuguese origin; appears to have arisen as a de novo mutation OTHER INFORMATION About 50% of the variant has the asparagine residue at position 80 deaminated REFERENCES 1. Wajcman, H., Kister, J., Vasseur, C., Blouquit, Y., Trastour, J.C., Cottenceau, D., and Galacteros, F.; Biochim. Biophys. Acta, 1138:127, 1992. Hb Providence beta82(EF6)Lys->Asn->Asp CONTACT 2,3-DPG contact HEMATOLOGY Mild polycythemia in the heterozygote ELECTROPHORESIS Two fast-moving Hb variants observed at alkaline pH; one (X-Asp) moves like Hb J, and the second (X-Asn) moves between Hb J and Hb A CHROMATOGRAPHY Both components can be isolated by DEAE-Sephadex chromatography; they also separate by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAT or AAC at codon 82 FUNCTION STUDIES Decreased oxygen affinity and 2,3-DPG binding; normal cooperativity STABILITY Normal OCCURRENCE Found in members of a Black family and in a Japanese family OTHER INFORMATION Quantity in the heterozygote: X-Asn 13-19%; X-Asp 32-33% REFERENCES 1. Moo-Penn, W.F., Jue, D.L., Bechtel, K.C., Johnson, M.H., Schmidt, M., McCurdy, P.R., Fox, J., Bonaventura, J., Sullivan, B., and Bonaventura, C.: J. Biol. Chem., 251:7557, 1976. 2. Bonaventura, J., Bonaventura, C., Sullivan, B., Ferruzzi, G., McCurdy, P., Fox, J., and Moo-Penn, W.F.: J. Biol. Chem., 251:7563, 1976. 3. Charache, S., Fox, J., McCurdy, P., Kazazian, H., Jr., and Winslow, R.: J. Clin. Invest., 59:652, 1977. 4. Harano, K.: Kawasaki Med. J., 8:1, 1982. Hb Rahere beta82(EF6)Lys->Thr CONTACT 2,3-DPG binding site HEMATOLOGY Mild polycythemia in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC or fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ACG at codon 82 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect and cooperativity; decreased 2,3-DPG binding STABILITY Normal OCCURRENCE Found in a Caucasian English male and a Japanese family OTHER INFORMATION Quantity in the heterozygote 48% REFERENCES 1. Lorkin, P.A., Stephens, A.D., Beard, M.E.J., Wrigley, P.F.M., Adams, L., and Lehmann, H.: Br. Med. J., 4:200, 1975. 2. Sugihara, J., Imamura, T., Nagafuchi, S., Bonaventura, J., Bonaventura, C., and Cashon, R.: J. Clin. Invest., 76:1169, 1985. Hb Helsinki beta82(EF6)Lys->Met CONTACT 2,3-DPG binding site HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; CNBr splitting; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ATG at codon 82 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and 2,3-DPG binding; normal cooperativity STABILITY Not reported OCCURRENCE Found in members of four different Finnish families OTHER INFORMATION Quantity in the heterozygote not reported REFERENCES 1. Ikkala, E., Koskela, J., Pikkarainen, P., Rahiala, E-L., El-Hazmi, M.A.F., Nagai, K., Lang, A., and Lehmann, H.: Acta Haematol., 56:257, 1976. Hb Ta-Li beta83(EF7)Gly->Cys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; a polymer of Hb X moves between Hb E and Hb G; the tetramer does not separate from Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography; Hb X elutes after Hb A STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; performic acid; sequencing DNA ANALYSES Not reported; presumed mutation GGC->TGC at codon 83 FUNCTION STUDIES Not reported STABILITY Slightly unstable; polymerization OCCURRENCE Found in members of a Chinese family living in Taiwan OTHER INFORMATION Quantity in the heterozygote 38-42% REFERENCES 1. Blackwell, R.Q., Liu, C-S., and Wang, C-L.: Biochim. Biophys. Acta, 243:467, 1971. Hb Pyrgos beta83(EF7)Gly->Asp CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH; excellent separation by IEF CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose and DEAE-Sephadex chromatography; Hb X and Hb A separate in cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC, fingerprinting, and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGC->GAC at codon 83 FUNCTION STUDIES Slightly increased oxygen affinity; normal Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in a Greek family, an African Black from the Republic of Mali, and in a family from Sicily, Italy OTHER INFORMATION Quantity in the heterozygote 35-40%; found in combination with Hb S REFERENCES 1. Tatsis, B., Sofroniadou, K., and Stergiopoulos, C.I.: Blood, 47:827, 1976. 2. Wajcman, H., Gacon, G., Tudury, C., Labie, D., Le Quintrec, Y., and Trinh Dinh, H.: Nouv. Rev. Fr. d'Hematol., 20:403, 1978. 3. Schiliro, G., Russo-Mancuso, G., Dibenedetto, S.P., Samperi, P., Di Cataldo, A., Ragusa, R., and Testa, R.: Hemoglobin, 15:431, 1991. Hb Muskegon beta83(EF7)Gly->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH; slightly anodic to Hb S; Hb X moves between Hb S and Hb C at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; cyanogen bromide treatment; sequencing of CNBr peptide DNA ANALYSES Not reported; presumed mutation GGC->CGC at codon 83 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a few members of an American family OTHER INFORMATION None; quantity in the heterozygote not reported REFERENCES 1. Broxson, E.H., Hine, T.K., and Moo-Penn, W.F.: Hemoglobin, 17:85, 1993. Hb Kofu beta84(EF8)Thr->Ile CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A do not separate at alkaline pH; best separation by IEF using narrow pH-range ampholytes; Hb X moves slightly faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation ACC->ATC at codon 84 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 73-year-old Japanese male OTHER INFORMATION Quantity of Hb X 48.5% REFERENCES 1. Harano, T., Harano, K., Ueda, S., Imai, N., and Kitazumi, T.: Hemoglobin, 10:417, 1986. Hb Buenos Aires beta85(F1)Phe->Ser ALSO KNOWN AS Bryn Mawr CONTACT External HEMATOLOGY Compensated hemolytic anemia; Heinz bodies present with oxidative agents ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH; a more intense minor Hb fraction is observed when stained with protein stains CHROMATOGRAPHY Hb X was isolated by DE-52 cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; thermolysin DNA ANALYSES Not reported; presumed mutation TTT->TCT at codon 85 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity STABILITY Unstable OCCURRENCE Found in members of an Argentinean family, and in a 19-year-old Caucasian female, not in her parents or siblings OTHER INFORMATION Quantity in the heterozygote 45-50% (protein stain); the Hb loses its heme group REFERENCES 1. de Weinstein, B.I., White, J.M., Wiltshire, B.G., and Lehmann, H.: Acta Haematol., 50:357, 1973. 2. Bradley, T.B., Wohl, R.C., Murphy, S.B., Oski, F.A., and Bunn, H.F.: Abstract, Blood, 40:947, 1972. Hb Olomouc beta86(F2)Ala->Asp CONTACT External HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; excellent separation by IEF; Hb X moves between Hb A and Hb F at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography; Hb X elutes faster than Hb A on cation exchange HPLC columns STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of tryptic peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 86 FUNCTION STUDIES Slightly increased oxygen affinity STABILITY Stable OCCURRENCE Found in members of a Czechoslovakian family and a Japanese family OTHER INFORMATION Quantity in the heterozygote 46-47% REFERENCES 1. Indrak, K., Wiedermann, B.F., Batek, F., Wilson, J.B., Webber, B.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 11:151, 1987. 2. Tagawa, Y., Fujinami, S., Kadota, Y., Nakagawa, T., Seki, T., Shiozaki, Y., Harano, T., Harano, K., and Ueda, S.: Hemoglobin, 16:73, 1992. Hb D-Ibadan beta87(F3)Thr->Lys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X has the mobility of Hb S); at acidic pH Hb X moves slightly slower than Hb A but much faster than Hb S CHROMATOGRAPHY Hb X and Hb A separate in both cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; chymotrypsin; sequencing DNA ANALYSES Not reported; presumed mutation ACA->AAA at codon 87 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a few Nigerian families and in a Black male in the USA OTHER INFORMATION Quantity in the heterozygote 41%; found in combination with Hb S and with deltabeta-thal REFERENCES 1. Watson-Williams, E.J., Beale, D., Irvine, D., and Lehmann, H.: Nature, 205:1273, 1965. 2. Falusi, A.G., Ogunmola, G.B., and Esan, G.J.F.: Clin. Res., 25:338A, 1977. 3. Rucknagel, D.L.: Hemoglobin, 3:77, 1979. Hb Valletta beta87(F3)Thr->Pro CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X was detected by IEF; Hb X moves between Hb S and Hb C CHROMATOGRAPHY The betaX chain elutes ahead of betaA in reversed phase HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES An ACA->CCA mutation at codon 87 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in many Maltese newborn babies and their parents, and also in some Italian newborn babies OTHER INFORMATION Ratio of Hb Valletta to Hb A in the newborn is 50:50; the Hb Valletta mutation occurs linked to the Hb F-Malta-I mutation (i.e. CAT->CGT) at codon 117 of the Ggamma gene (the two mutations are 27-28 kb apart) REFERENCES 1. Kutlar, F., Felice, A.E., Grech, J.L., Bannister, W.H., Kutlar, A., Wilson, J.B., Webber, B.B. Hu, H. , and Huisman, T.H.J.: Hum. Genet., 86:591, 1991. Hb Quebec-Chori beta87(F3)Thr->Ile CONTACT External HEMATOLOGY Not reported; presumably normal in the heterozygote ELECTROPHORESIS No separations at alkaline pH and by IEF CHROMATOGRAPHY The betaX, betaA, and betaS chains readily separate by reversed phase HPLC (betaX elutes between betaA and alpha) STRUCTURE STUDIES Tryptic digestion of AE-globin X; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing by liquid secondary ion mass spectrometry DNA ANALYSES Not reported; presumed mutation ACA->ATA at codon 87 FUNCTION STUDIES Normal STABILITY Not reported OCCURRENCE Found in a 3-year-old girl and her mother (of English-Irish-French-Canadian extraction); the father was from Ghana OTHER INFORMATION Occurred in association with Hb S; this compound heterozygote has a mild to moderately severe sickle cell disease; quantity in the heterozygote not reported but appears to be ~40% by reversed phase HPLC; quantities of Hb X and Hb S in the compound heterozygote estimated at 60% (Hb X) and 40% (Hb S); the beta87(F3) amino acid is important as an interaction site with beta6(A3) (Glu->Val in Hb S) in polymerization upon deoxygenation; the introduction of isoleucine increases this interaction REFERENCES 1. Witkowska, H.E., Lubin, B.H., Beuzard, Y., Baruchel, S., Esseltine, D.W., Vichinsky, E.P., Kleman, K.M., Bardakdjian-Michau, J., Pinkoski, L., Cahn, S., Roitman, E., Green, B.N., Falick, A.M., and Shackleton, C.H.L.: N. Engl. J. Med., 325:1150, 1991. Hb Boras beta88(F4)Leu->Arg CONTACT Heme contact HEMATOLOGY Moderately severe hemolytic anemia; Heinz bodies ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH CHROMATOGRAPHY Hb X elutes behind Hb A2 on a cation exchange HPLC column; the betaX and betaA chains separate on a reversed phase HPLC column (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC or fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG at codon 88 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in members of a Swedish family and a young South African female (her parents are both normal) OTHER INFORMATION Quantity in the heterozygote ~25% REFERENCES 1. Hollender, A., Lorkin, P.A., Lehmann, H., and Svenson, B.: Nature, 222:953, 1969. 2. Bird, A.R., Elliot, T.E., Wilson, J.B., Webber, B.B., Kutlar, F., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 11:157, 1987. Hb Santa Ana beta88(F4)Leu->Pro CONTACT Heme contact HEMATOLOGY Moderately severe hemolytic anemia; reticulocytosis; Heinz bodies ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH (Hb X appears as a smear between Hb A2 and Hb A); a free alpha chain band is also present CHROMATOGRAPHY Not reported STRUCTURE STUDIES Fingerprinting; amino acid analysis DNA ANALYSES A CTG->CCG mutation at codon 88 (Ref. 5) FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in three members of a family living in California, in a 7-year-old male living in Hungary, in members of a family living in the USA, in a patient living in France, and in a Caucasian female from Brazil OTHER INFORMATION Hb X occurred in some families as a de novo mutation; the Brazilian patient carried an additional mutation at codon 9 (TCT->TGT) (= Hb Porto Alegre); quantity in the heterozygote not definitely determined REFERENCES 1. Opfell, R.W., Lorkin, P.A., and Lehmann, H.: J. Med. Genet., 5:292, 1968. 2. Fairbanks, V.F., Opfell, R.W., and Burgert, E.M.: Am. J. Med., 46:344, 1969. 3. Hollan, S.R., Szelenyi, J.G., Miltenyi, M., Charlesworth, D., Lorkin, P.A., and Lehmann, H.: Haematologia, 4:141, 1970. 4. Biserte, G., Goudemand, M., Voisin, D., Charlesworth, D., Lorkin, P.A., and Lehmann, H.: Nouv. Rev. Fr. d'Hematol., 10:201, 1970. 5. Goncalves, M.S., Sonati, M.F., Kimura, M., Arruda, V.R., Costa, F.F., Nechtman, J.F., and Stoming, T.A.: Hemoglobin, 18:235, 1994. Hb Creteil beta89(F5)Ser->Asn CONTACT Internal HEMATOLOGY Severe erythrocytosis in the heterozygote (PCV 0.65 l/l) ELECTROPHORESIS No separation of Hb X and Hb A with conventional techniques; separation is possible by IEF CHROMATOGRAPHY Hb X can be isolated by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AGT->AAT at codon 89 FUNCTION STUDIES Greatly increased oxygen affinity; decreased Bohr effect; markedly reduced cooperativity; does not interact with 2,3-DPG STABILITY Normal OCCURRENCE Found in two members of a family from Southern France OTHER INFORMATION Quantity in the heterozygote 30% REFERENCES 1. Thillet, J., Blouquit, Y., Garel, M.C., Dreyfus, B., Reyes, F., Cohen-Solal, M., Beuzard, Y., and Rosa, J.: J. Mol. Med., 1:135, 1976. 2. Poyart, C., Bursaux, E., Teisseire, B., Freminet, A., Duvelleroy, M., and Rosa, J.: Ann. Int. Med., 88:758, 1978. 3. Arnone, A., Thillet, J., and Rosa, J.: J. Biol. Chem., 256:8545, 1981. Hb Vanderbilt beta89(F5)Ser->Arg CONTACT Internal HEMATOLOGY Severe erythrocytosis in the heterozygote (PCV 0.64 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb F; Hb X moves like Hb S at acidic pH CHROMATOGRAPHY Hb X can be isolated by DEAE-Sephadex chromatography; it elutes before Hb A STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AGT->CGT at codon 89 FUNCTION STUDIES Greatly increased oxygen affinity; decreased sensitivity to 2,3-DPG STABILITY Not reported OCCURRENCE Found in members of a Caucasian family living in Tennessee, USA OTHER INFORMATION Quantity in the heterozygote not reported; it may be as high as 40% REFERENCES 1. Paniker, N.V., Lin, K-T.D., Krantz, S.B., Flexner, J.M., Wasserman, B.K., and Puett, D.: Br. J. Haematol., 39:249, 1978. Hb Villaverde beta89(F5)Ser->Thr CONTACT Internal HEMATOLOGY Severe erythrocytosis in the heterozygote (PCV 0.624 l/l) ELECTROPHORESIS No separation by standard techniques CHROMATOGRAPHY Not reported STRUCTURE STUDIES The betaX and betaA chains were digested with trypsin; tryptic peptides were separated by reversed phase HPLC; peptides identified by mass spectrometry and amino acid analysis DNA ANALYSES Not reported; presumed mutation AGT->ACT at codon 89 FUNCTION STUDIES Greatly increased oxygen affinity; markedly reduced cooperativity STABILITY Not reported OCCURRENCE Found in a 41-year-old male born in Spain OTHER INFORMATION Quantity in the heterozygote is unknown REFERENCES 1. Wajcman, H., Kister, J., Prome, D., Galacteros, F., and Gilsanz, F.: Biochim. Biophys. Acta, 1225:89, 1993. Hb Agenogi beta90(F6)Glu->Lys CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves close to Hb A2 CHROMATOGRAPHY Hb X elutes behind Hb A2 from a cation exchange HPLC column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->AAG at codon 90 FUNCTION STUDIES Slightly reduced oxygen affinity; normal Bohr effect and cooperativity STABILITY Slightly reduced OCCURRENCE Found in a Japanese family, a Black American family, and a Hungarian family OTHER INFORMATION Quantity in the heterozygote 36.5-40.5%; occurred in association with a betao-thal REFERENCES 1. Miyaji, T., Suzuki, H., Ohba, Y., and Shibata, S.: Clin. Chim. Acta, 14:624, 1966. 2. Imai, K., Morimoto, H., Kotani, M., Shibata, S., Miyaji, T., and Matsutomo, K.: Biochim. Biophys. Acta, 200:197, 1970. 3. Castro, O., Winter, W.P., Doan, R.J., Lee, C.K., and Rucknagel, D.L.: Clin. Res., 24:630A, 1976. 4. Corso, D., Cognata, B., Ciaccio, C., Piazza, T., Dibenedetto, S.P., Samperi, P., Russo Mancuso, G., and Schiliro, G.: Hemoglobin, 14:549, 1990. Hb Roseau-Pointe a Pitre beta90(F6)Glu->Gly CONTACT External HEMATOLOGY About normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X takes the position of Hb D; excellent separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GGG at codon 90 FUNCTION STUDIES Decreased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a Dominican newborn and his mother OTHER INFORMATION Occurred in association with a beta-thal; quantity in the heterozygote 36%; the mother may have an alpha-thal explaining a most modest anemia with microcytosis and hypochromia REFERENCES 1. Merault, G., Keclard, L., Saint-Martin, C., Jasmin, K., Campier, A., Delanoe-Garin, J., Arous, N., Fortune, R., Theodore, M., Seytor, S., Rosa, J., Blouquit, Y., and Galacteros, F.: FEBS Lett., 184:10, 1985. Hb Pierre-Benite beta90(F6)Glu->Asp CONTACT External HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.56 l/l) ELECTROPHORESIS No separations with standard techniques; IEF showed a double Hb A band CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-beta chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GAC or GAT at codon 90 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in members of a Caucasian family from Northern France OTHER INFORMATION Quantity in the heterozygote 40-47% (densitometry) REFERENCES 1. Baklouti, F., Giraud, Y., Francina, A., Richard, G., Favre-Gilly, J., and Delaunay, J.: Hemoglobin, 12:171, 1988. Hb Sabine beta91(F7)Leu->Pro CONTACT Heme contact HEMATOLOGY Hemolytic anemia in the heterozygote; reticulocytosis; Heinz bodies ELECTROPHORESIS Two Hb fractions move between Hb A2 and Hb S at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of tryptic peptides by cation exchange chromatography; amino acid analysis; thermolysin DNA ANALYSES Not reported; presumed mutation CTG->CCG at codon 91 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 16-year-old Scottish-English-German female but not in her parents or siblings; also in a 7-year-old Yugoslavian boy but not in his parents OTHER INFORMATION Quantity in the heterozygote was estimated at 8% REFERENCES 1. Schneider, R.G., Ueda, S., Alperin, J.B., Brimhall, B., and Jones, R.T.: N. Engl. J. Med., 280:739, 1969. 2. Mills, G.C., Alperin, J.B., Hill, F.L., and Henderson, R.J.; Biochem. Med., 5:212, 1971. 3. Shaeffer, J.R., J. Biol. Chem., 248:7473, 1973. 4. Bogoevski, P., Efremov, G.D., Kezic, J., Lam, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 7:195, 1983. Hb Caribbean beta91(F7)Leu->Arg CONTACT Heme contact HEMATOLOGY Mild anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X migrates slightly faster than Hb S CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column; Hb X separates from Hb A and Hb A2 on a cation exchange HPLC column; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC or by fingerprinting; amino acid analysis DNA ANALYSES A CTG->CGG mutation at codon 91 (Ref. 3) FUNCTION STUDIES Decreased oxygen affinity; normal Bohr effect STABILITY Mildly unstable OCCURRENCE Found in a few families living in Jamaica and Canada OTHER INFORMATION Quantity in the heterozygote 39-44%; found in association with Hb S; the S-Caribbean compound heterozygosity is not associated with serious clinical manifestations REFERENCES 1. Ahern, E., Ahern, V., Hilton, T., Serjeant, G.R., Serjeant, B.E., Seakins, M., Lang, A., Middleton, A., and Lehmann, H.; FEBS Lett., 69:99, 1976. 2. Ali, M.A.M., Pinkerton, P., Chow, S.W.S., Zaetz, S.D., Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 12:137, 1988. 3. Waye, J.S., Patterson, M., Eng, B., Chui, D.H.K., Sher, G.D., and Olivieri, N.F.: Am. J. Hematol., 47:33, 1994. Hb Mozhaisk beta92(F8)His->Arg CONTACT Heme contact; proximal histidine HEMATOLOGY Moderately severe hemolytic anemia and reticulocytosis in the heterozygote; Heinz bodies ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slower than Hb A; excellent separation by IEF CHROMATOGRAPHY No separations reported except by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC or by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC at codon 92 FUNCTION STUDIES Slightly increased oxygen affinity; no cooperativity; increased 2,3-DPG content STABILITY Unstable OCCURRENCE Found in a 9-year-old Russian male and in a young South African male of mixed ethnic origin, and in his brother and father OTHER INFORMATION Quantity in the heterozygote 25-30% based on stability REFERENCES 1. Spivak, V.A., Molchanova, T.P., Postnikov, Yu.V., Aseeva, E.A., Lutsenko, I.N., and Tokarev, Yu.N.: Hemoglobin, 6:169, 1982. 2. Bird, A.R., Elliott, T., Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 13:193, 1989. Hb M-Hyde Park beta92(F8)His->Tyr ALSO KNOWN AS M-Akita CONTACT Heme contact; proximal histidine HEMATOLOGY Hereditary cyanosis (ferriHb) in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slightly ahead of Hb A2 CHROMATOGRAPHY Hb X and Hb A can be separated by anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of the AE-betaX chain; separation of peptides by cation exchange chromatography or by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->TAC at codon 92 FUNCTION STUDIES Normal oxygen affinity STABILITY Unstable; dissociation into dimers OCCURRENCE Found in a Black subject living in the USA, a Japanese family, members of a Yugoslavian family, a Caucasian female of Norwegian-German ancestry as a de novo mutation OTHER INFORMATION Patients often misdiagnosed as having cyanotic heart disease; quantity in the heterozygote 23-32% REFERENCES 1. Heller, P., Coleman, R.D., and Yakulis, V.: J. Clin. Invest., 45:1021, 1966. 2. Ranney, H.M., Nagel, R.L., Heller, P., and Udem, L.: Biochim. Biophys. Acta, 160:112, 1968. 3. Shibata, S., Miyaji, T., Iuchi, I., Ohba, Y., and Yamamoto, K.: J. Biochem., 63:193, 1968. 4. Shibata, S., Yamamoto, K., Ohba, Y., Miyaji, T., Karita, K., and Iuchi, I.: Acta Haematol. Jpn., 32:311, 1969. 5. Efremov, G.D., Huisman, T.H.J., Stanulovic, M., Zurovec, M., Duma, H., Wilson, J.B., and Jeremic, V.: Scand. J. Haematol., 13:48, 1974. 6. Stamatoyannopoulos, G., Nute, P.E., Giblett, E., Detter, J., and Chard, R.: J. Med. Genet., 13:142, 1976. 7. Yamada, T., Marini, C.P., and Cassatt, J.C., Biochemistry, 17:231, 1978. Hb Newcastle beta92(F8)His->Pro CONTACT Heme contact; proximal histidine HEMATOLOGY Mild chronic anemia with Heinz bodies present after splenectomy ELECTROPHORESIS Hb X moves between Hb A and Hb A2 at alkaline pH CHROMATOGRAPHY Hb X can be isolated by DEAE-Sephadex chromatography; Hb X elutes between Hb A2 and Hb A STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CCC at codon 92 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 67-year-old English female OTHER INFORMATION Quantity in the heterozygote not reported; metHb was not observed REFERENCES 1. Finney, R., Casey, R., Lehmann, H., and Walker, W.: FEBS Lett., 60:435, 1975. Hb Saint Etienne beta92(F8)His->Gln ALSO KNOWN AS Istanbul CONTACT Heme contact; proximal histidine HEMATOLOGY Hemolytic anemia of variable severity in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb S and Hb C CHROMATOGRAPHY Hb X can be isolated by DEAE-Sephadex chromatography; Hb X elutes before Hb A STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CAA or CAG at codon 92 FUNCTION STUDIES Normal oxygen affinity for whole cells; increased oxygen affinity for 'stripped' pure Hb X; no Bohr or 2,3-DPG effects; decreased cooperativity STABILITY Unstable; dissociates into dimers, particularly at higher pH OCCURRENCE Found in a young French male and in a Turkish male, but not in their parents OTHER INFORMATION Variant carries heme only on its alpha chains; this affects quantitation of the abnormal Hb; quantity in heterozygotes estimated at 25% which is likely too low; high level (20%) of Hb F present in the French patient with the least severe disease REFERENCES 1. Cohen-Solal, M., Thillet, J., Gailardon, J., and Rosa, J.: Eur. J. Clin. Biol. Res., 17:988, 1970. 2. Aksoy, M., Erdem, S., Efremov, G.D., Wilson, J.B., Huisman, T.H.J., Schroeder, W.A., Shelton, J.R., Shelton, J.B., Ulutin, O.N., and Muftuoglu, A.: J. Clin. Invest., 51:2380, 1972. 3. Beuzard, Y., Courvalin, J.Cl., Cohen-Solal, M., Garel, M.C., and Rosa, J.: FEBS Lett., 27:76, 1972. 4. Rosa, J., Brizard, C.P., Gibaud, A., Beuzard, Y., Courvalin, J.Cl., Cohen-Solal, M., Garel, M.C., and Thillet, J.: Nouv. Rev. Fr. d'Hematol., 12:691, 1972. Hb J-Altgeld Gardens beta92(F8)His->Asp CONTACT Heme contact; proximal histidine HEMATOLOGY Mild anemia in the proband who had Hb X-betao-thal ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Not reported; the betaX and betaA chains readily separate by CM-cellulose chromatography (the Clegg method) STRUCTURE STUDIES Tryptic digestion of the betaX chain; separation of peptides by fingerprinting; cation exchange chromatography; glycinamidation; amino acid analysis; formic acid DNA ANALYSES Not reported; presumed mutation CAC->GAC at codon 92 FUNCTION STUDIES Normal oxygen affinity; cooperativity slightly decreased STABILITY Mildly unstable OCCURRENCE Found in a 21-year-old Black female and her son living in Chicago, Illinois, USA OTHER INFORMATION Methemoglobinemia was absent REFERENCES 1. Adams, J.G., III, Przywara, K.P., Heller, P., and Shamsuddin, M.: Hemoglobin, 2:403, 1978. Hb Redondo beta92(F8)His->Asn->Asp ALSO KNOWN AS Isehara CONTACT Heme contact; proximal histidine HEMATOLOGY Chronic hemolytic anemia in the heterozygote; reticulocytosis ELECTROPHORESIS Hb X and Hb A separate at alkaline pH and by IEF; one band (X-Asn) was close to Hb A2, and the second (X-Asp) was between Hb A2 and Hb F CHROMATOGRAPHY Two betaX chains separate from betaA by CM-cellulose chromatography and by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of the AE-betaX chain; separation of the peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A CAC->AAC mutation at codon 92 FUNCTION STUDIES Oxygen dissociation curves were performed on stripped lysate (pH 7.2) and showed a slight decrease of the P50 value and a decrease of n50 in relation to the biphasic shape of the curve STABILITY Unstable OCCURRENCE Found as a de novo mutation in a Portuguese male and a Japanese female and her daughter OTHER INFORMATION No metHb formation; Hb X readily loses its heme group; quantity of the two compounds in the heterozygote not reported REFERENCES 1. Wajcman, H., Vasseur, C., Blouquit, Y., Esperito Santo, D., Peres, M.J., Martins, M.C., Poyart, C., and Galacteros, F.: Am. J. Hematol., 38:194, 1991. 2. Harano, T., Harano, K., Kushida, Y., Ueda, S., Yoshii, A., and Nishinarita, M.: Hemoglobin, 15:279, 1991. Hb Okazaki beta93(F9)Cys->Arg CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves slower than Hb A; excellent separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGT->CGT at codon 93 FUNCTION STUDIES Increased oxygen affinity; Bohr effect slightly decreased STABILITY Unstable OCCURRENCE Found in a healthy, 45-year-old Japanese male OTHER INFORMATION Quantity in the heterozygote 40-41% REFERENCES 1. Harano, K., Harano, T., Shibata, S., Ueda, S., Mori, H., and Seki, M.: FEBS Lett., 173:45, 1984. Hb Barcelona beta94(FG1)Asp->His CONTACT External HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves slower than Hb A; excellent separation by IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography and reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->CAC at codon 94 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Not reported OCCURRENCE Found in a Spanish family OTHER INFORMATION Quantity in the heterozygote 37% REFERENCES 1. Wajcman, H., Aguilar, I., Bascompte, J.L., Labie, D., Poyart, C., and Bohn, B.: J. Mol. Biol., 156:185, 1982. 2. Phillips, S.E.V., Perutz, M.F., Poyart, C., and Wajcman, H.: J. Mol. Biol., 164:477, 1983. Hb Bunbury beta94(FG1)Asp->Asn CONTACT External HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is located in the position of Hb F; at acidic pH it moves between Hb A and Hb S CHROMATOGRAPHY Hb X can be isolated by DE-52 cellulose chromatography STRUCTURE STUDIES Tryptic digestion of the betaX chain; separation of the peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC at codon 94 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect STABILITY Normal OCCURRENCE Found in an Italian family in Australia and in a Caucasian family in Philadelphia, PA, USA OTHER INFORMATION Quantity in the heterozygote 38-40% REFERENCES 1. Como, P.F., Kennett, D., Wilkinson, T., and Kronenberg, H.: Hemoglobin, 7:413, 1983. 2. Ballas, S.K., Park, D., Fernandez, L., Hine, T.K., Jue, D.L., Johnson, M.H., and Moo-Penn, W.F.: Hemoglobin, 16:281, 1992. Hb Chandigarh beta94(FG1)Asp->Gly CONTACT External HEMATOLOGY Normal Hb level but microcytosis and hypochromia in the proband who is compound heterozygous for Hb X and a betao-thal ELECTROPHORESIS Hb X moves slowly at alkaline pH with a mobility between Hb F and Hb S; excellent separation by IEF CHROMATOGRAPHY Hb X did not separate from Hb A2 by cation exchange HPLC; CM-cellulose chromatography separated the betaA, betaX, and alpha chains STRUCTURE STUDIES The betaX chain was digested with trypsin and the resulting soluble tryptic peptides were separated by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->GGC at codon 94 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a healthy Indian male OTHER INFORMATION The proband is the father of a thalassemic child REFERENCES 1. Dash, S., Wilson, J.B., Webber, B.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 13:749, 1989. Hb N-Baltimore beta95(FG2)Lys->Glu ALSO KNOWN AS Hopkins-I; Jenkins; N-Memphis; Kenwood CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is one of the fastest moving beta chain variants; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A separate by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; cation exchange chromatography; reversed phase HPLC; amino acid analysis DNA ANALYSES An AAG->GAG mutation at codon 95 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in numerous Black families in the SE-USA OTHER INFORMATION Quantity in the heterozygotes 44-54%; found in combination with Hb C and also with Hb S REFERENCES 1. Clegg, J.B., Naughton, M.A., and Weatherall, D.J.: Nature, 207:945, 1965. 2. Dobbs, N.B., Simmons, J.W., Wilson, J.B., and Huisman, T.H.J.: Biochim. Biophys. Acta, 117:492, 1966. 3. Fuller, R.W. and Hunt, J.M.: Nature, 214:189, 1967. 4. Johnson, C., Powars, D., and Schroeder, W.A.: Acta Haematol., 56:183, 1976. Hb J-Cordoba beta95(FG2)Lys->Met CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; no separation at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->ATG at codon 95 FUNCTION STUDIES Slightly increased oxygen affinity; decreased cooperativity STABILITY Stable OCCURRENCE Found in a 1-year-old girl born in Cordoba, Argentina OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Bardakdjian, J., Kister, J., Rhoda, M.D., Marden, M., Arous, N., De Leon, J., North, M.L., Lacombe, C., Blouquit, Y., Castracane, C., Riou, J., Rosa, J., and Galacteros, F.: Hemoglobin, 12:1, 1988. Hb Detroit beta95(FG2)Lys->Asn CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; no separation at acidic pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; fingerprinting; cation exchange chromatography; amino acid analysis; sequence by Sequenator; HPLC DNA ANALYSES Not reported; presumed mutation AAG->AAC or AAT at codon 95 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in a 30-year-old Indian female living in the USA OTHER INFORMATION Quantity in the heterozygote ~48% REFERENCES 1. Moo-Penn, W.F., Schneider, R.G., Andrian, S., and Das, D.K.: Biochim. Biophys. Acta, 536:283, 1978. Hb Regina beta96(FG3)Leu->Val CONTACT Heme contact HEMATOLOGY Mild erythrocytosis in the heterozygote ELECTROPHORESIS None of the available electrophoretic procedures allowed the separation of Hb X and Hb A CHROMATOGRAPHY Hb X and Hb A separate by cation exchange HPLC (Hb X elutes behind Hb A) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A CTG->GTG mutation at codon 96 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a Caucasian male of Scandinavian descent OTHER INFORMATION Quantity in the heterozygote ~40% REFERENCES 1. Devaraj, R., Wilson, J.B., and Huisman, T.H.J.: Am. J. Hematol., 19:195, 1985. Hb Malmo beta97(FG4)His->Gln CONTACT External; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by standard techniques; partial resolution by IEF CHROMATOGRAPHY Hb X can be separated from Hb A by DEAE-Sephadex chromatography; Hb X elutes after, but not well-separated from Hb A STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC or by fingerprinting; amino acid analysis; sequencing DNA ANALYSES A CAC->CAA and a CAC->CAG mutation at codon 97; two different mutations observed in two unrelated Swedish families (Ref. 4) FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in several Swedish, English, and German families OTHER INFORMATION Quantity in the heterozygote 48% REFERENCES 1. Lorkin, P.A., Lehmann, H., Fairbanks, V.F., Berglund, G., and Leonhardt, T.: Biochem. J., 119:68, 1970. 2. Boyer, S.H., Charache, S., Fairbanks, V.F., Maldonado, J.E., Noyes, A., and Gayle, E.E.: J. Clin. Invest., 51:666, 1972. 3. Zak, S.J., Geller, G.R., Krivit, W., Tukey, D., Brimhall, B., Jones, R.T., Bunn, H.F., and McCormack, M.: Br. J. Haematol., 33:101, 1976. 4. Landin, B., Berglund, S., and Wallman, K.: Am. J. Hematol., 51:32, 1996. Hb Wood beta97(FG4)His->Leu CONTACT External; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by standard techniques; separation is possible by IEF CHROMATOGRAPHY Hb X can be isolated by cation exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CTC at codon 97 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in a family of Swedish-Norwegian descent OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Taketa, F., Huang, Y.P., Libnoch, J.A., and Dessel, B.H.: Biochim. Biophys. Acta, 400:348, 1975. 2. Taketa, F., Antholine, W.E., Mauk, A.G., and Libnoch, J.A.: Biochemistry, 14: 3229, 1975. Hb Nagoya beta97(FG4)His->Pro CONTACT External; alpha1beta2 contact HEMATOLOGY Chronic hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X focuses slightly more anodic than Hb A by IEF CHROMATOGRAPHY The betaX chain coeluted with the alphaA chain in reversed phase HPLC STRUCTURE STUDIES pCMB precipitation; tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CCC at codon 97 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity STABILITY Unstable OCCURRENCE Found in members of a Japanese family OTHER INFORMATION Quantity in the heterozygote 16.7 and 25.5%; variant susceptible to oxidation; it loses heme during that process REFERENCES 1. Ohba, Y., Imanaka, M., Matsuoka, M., Hattori, Y., Miyaji, T., Funaki, C., Shibata, S., Shimokata, H., Kuzuya, F., and Miwa, S.: Hemoglobin, 9:11, 1985. Hb Moriguchi beta97(FG4)His->Tyr CONTACT External; alpha1beta2 contact HEMATOLOGY Normal in the heterozygote; no erythrocytosis ELECTROPHORESIS Hb X and Hb A separate by IEF; no separation by standard techniques CHROMATOGRAPHY Hb X and Hb A separate by anion exchange HPLC; the betaX and betaA chains separate by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of the AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->TAC at codon 97 FUNCTION STUDIES Slightly increased oxygen affinity; Bohr effect nearly normal STABILITY Stable OCCURRENCE Found in a diabetic Japanese female and her 27-year-old son OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Ohba, Y., Imai, K., Kumada, I., Ohsawa, A., and Miyaji, T.: Hemoglobin, 13:367, 1989. Hb Koln beta98(FG5)Val->Met ALSO KNOWN AS San Francisco (Pacific); Ube-I CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Mild hemolytic anemia in the heterozygote; reticulocytosis; Heinz body formation ELECTROPHORESIS Hb X moves as a multiple Hb component between Hb A and Hb A2 in various media at alkaline pH CHROMATOGRAPHY Hb X can be isolated by DEAE-Sephadex or CM-Sephadex chromatography; chains can best be separated by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of AE-beta chain; separation of peptides by fingerprinting; cation exchange HPLC; reversed phase HPLC; amino acid analysis DNA ANALYSES A GTG->ATG mutation at codon 98 FUNCTION STUDIES Increased oxygen affinity; no cooperativity; normal 2,3-DPG effect STABILITY Unstable OCCURRENCE Hb Koln is found in various racial and ethnic groups; it is the most common unstable Hb, often observed as a de novo mutation OTHER INFORMATION Quantity in the heterozygote not accurately determined REFERENCES 1. Pribilla, W., Klesse, P., Betke, K., Lehmann, H., and Beale, D.: Klin. Wschr., 43: 1049, 1965. 2. Carrell, R.W., Lehmann, H., and Hutchinson, H.E., Nature, 210:915, 1966. 3. Ohba, Y.: Hemoglobin, 14:353, 1990. Hb Nottingham beta98(FG5)Val->Gly CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Severe hemolytic anemia; reticulocytosis; Heinz bodies ELECTROPHORESIS Hb X moves slightly faster then Hb A2 at alkaline pH CHROMATOGRAPHY Hb X separates from Hb A by DEAE-cellulose chromatography; the betaX chain separates completely from the other chains by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; peptides were separated by reversed phase HPLC or fingerprinting; amino acid analysis; sequencing DNA ANALYSES A GTG->GGG mutation at codon 98 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity STABILITY Unstable OCCURRENCE Found in a 2-year-old English female, in a 7-year-old Caucasian male from North Carolina, and in a 7-year-old Canadian male; all three are apparently de novo mutations OTHER INFORMATION Quantity in the heterozygote ~26% REFERENCES 1. Gordon-Smith, E.C., Dacie, J.V., Blecher, T.E., French, E.A., Wiltshire, B.G., and Lehmann, H.: Proc. Roy. Soc. Med., 6:507, 1973. 2. Orringer, E.P., Felice, A.E., Reese, A., Wilson, J.B., Lam, H., Gravely, M.E., and Huisman, T.H.J.: Hemoglobin, 2:315, 1978. 3. Cepreganova, B., Wilson, J.B., Huisman, T.H.J., and Hume, H.A.: Hemoglobin, 16:77, 1992. Hb Djelfa beta98(FG5)Val->Ala CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Normal but with a modest reticulocytosis and Heinz body formation ELECTROPHORESIS Hb X moves anodal to Hb A2 at alkaline pH and by IEF CHROMATOGRAPHY The betaX chain separates completely from the other chains by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC or by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTG->GCG at codon 98 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Unstable OCCURRENCE Found in two unrelated Caucasian adults but not in their parents OTHER INFORMATION Quantity in the heterozygote 36% REFERENCES 1. Gacon, G., Wajcman, H., Labie, D., and Cosson, A.: FEBS Lett., 58:238, 1975. 2. Gacon, G., Krishnamoorthy, R., Wajcman, H., Labie, D., Tapon, J., and Cosson, A.: Biochim. Biophys. Acta, 490:156, 1977. 3. Bird, A.R., Elliott, T., Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 13:193, 1989. Hb Mainz beta98(FG5)Val->Glu CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Severe hemolytic anemia ELECTROPHORESIS Several slow moving bands observed at alkaline pH CHROMATOGRAPHY Not reported; betaX and betaA appear to separate on a reversed phase HPLC column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTG->GAG at codon 98 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 5-year-old German child; parents were not available for study OTHER INFORMATION Hb X readily loses heme; the same is the case for Hb Nottingham REFERENCES 1. Wajcman, H., Behnken, L.J., Riou, J., and Galacteros, F.: Abstract 258, Br. J. Haematol., 87:66 (Suppl. 1), 1994. Hb Kempsey beta99(G1)Asp->Asn CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.52-0.63 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves about as Hb F; Hb X moves like Hb S at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 99 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Not reported OCCURRENCE Found in members of a family of Irish descent; a male of French ancestry, and in two Black families OTHER INFORMATION Quantity in the heterozygote 45-48% REFERENCES 1. Reed, C.S., Hampson, R., Gordon, S., Jones, R.T., Novy, M.J., Brimhall, B., Edwards, M.J., and Koler, R.D.: Blood, 31:623, 1968. 2. Ogata, R.T. and McConnell, H.M.: Biochemistry, 11:4792, 1972. 3. Lindstrom, T.R., Baldassare, J.J., Bunn, H.F., and Ho, C.: Biochemistry, 12: 4212, 1973. 4. Bunn, H.F., Wohl, R.C., Bradley, T.B., Cooley, M., and Gibson, Q.H.: J. Biol. Chem., 249:7402, 1974. 5. Nagai, M., Nishibu, M., Sugita, Y., Yoneyama, Y., Jones, R.T., and Gordon, S.: J. Biol. Chem., 250:3169, 1975. Hb Yakima beta99(G1)Asp->His CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.45-0.55 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb F; Hb X moves between Hb A and Hb S, closer to Hb S, at acidic pH CHROMATOGRAPHY Hb X and Hb A were separated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; carboxypeptidase A and B; leucine amino peptidase; sequencing DNA ANALYSES Not reported; presumed mutation GAT->CAT at codon 99 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Stable OCCURRENCE Found in three members of a Caucasian family OTHER INFORMATION Quantity in the heterozygote 38.5%; father, a heterozygote, developed acute nonlymphocytic leukemia following years of treatment with 32P REFERENCES 1. Jones, R.T., Osgood, E.E., Brimhall, B., and Koler, R.D.: J. Clin. Invest., 46: 1840, 1967. 2. Novy, M.J., Edwards, M.J., and Metcalfe, J.: J. Clin. Invest., 46:1848, 1967. 3. Bagby, G.C., Jr., Richert-Boe, K., and Koler, R.D.: Blood, 52:350, 1978. Hb Radcliffe beta99(G1)Asp->Ala CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.48-0.58 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; the major Hb X band moves just ahead of Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides was by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAT->GCT at codon 99 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity and Bohr effect STABILITY Abnormal polymerization OCCURRENCE Found in three members of an English family OTHER INFORMATION Quantity in the heterozygote not reported REFERENCES 1. Weatherall, D.J., Clegg, J.B., Callender, S.T., Wells, R.M.G., Gale, R.E., Huehns, E.R., Perutz, M.F., Viggiano, G., and Ho, C.: Br. J. Haematol., 35:177, 1977. Hb Ypsilanti (Ypsi) beta99(G1)Asp->Tyr CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.46-0.63 l/l) ELECTROPHORESIS Two components are present at alkaline pH: one moves in the position of Hb F, and the other moves between Hb A and Hb F CHROMATOGRAPHY Not reported STRUCTURE STUDIES No details provided DNA ANALYSES Not reported; presumed mutation GAT->TAT at codon 99 FUNCTION STUDIES Increased oxygen affinity STABILITY Polymerization OCCURRENCE Found in 17 members in three generations of a Black family OTHER INFORMATION Quantity in the heterozygote: two components are present, one for 15% and the other for 25% REFERENCES 1. Rucknagel, D.L., Glynn, K.P., and Smith, J.R.: Clin. Res., 15:270, 1967. 2. Glynn, K.P., Penner, J.A., Smith, J.R., and Rucknagel, D.L.: Ann. Int. Med., 69: 769, 1968. Hb Hotel-Dieu beta99(G1)Asp->Gly CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.42-0.63 l/l) ELECTROPHORESIS Hb X migrates slightly slower than Hb F at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephacel chromatography; Hb X elutes free of Hb A2 and Hb A STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->GGT at codon 99 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity STABILITY Not reported OCCURRENCE Found in three members of a Caucasian French family OTHER INFORMATION Quantity in the heterozygote 38-48% REFERENCES 1. Blouquit, Y., Braconnier, F., Galacteros, F., Arous, N., Soria, J., Zittoun, R., and Rosa, J.: Hemoglobin, 5:19, 1981. Hb Chemilly beta99(G1)Asp->Val CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.55 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves as Hb F; no separation at acidic pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAT->GTT at codon 99 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Not reported OCCURRENCE Found in a 35-year-old French Caucasian female OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Rochette, J., Poyart, C., Varet, B., and Wajcman, H.: FEBS Lett., 166:8, 1984. Hb Coimbra beta99(G1)Asp->Glu ALSO KNOWN AS Ingelheim CONTACT Internal; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.52-0.62 l/l) ELECTROPHORESIS No separation obtained by standard techniques or by IEF CHROMATOGRAPHY Hb X was detected because the betaX chain eluted ahead of betaX in a reversed phase chromatogram STRUCTURE STUDIES Tryptic digestion of AE-betaX+betaA chains; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAT->GAA or GAG at codon 99 FUNCTION STUDIES Increased oxygen affinity STABILITY Stable OCCURRENCE Found in a 60-year-old Portuguese male and his son, and in several members of a large German family OTHER INFORMATION Quantity in the heterozygote 48% REFERENCES 1. Tamagnini, G.P., Ribeiro, M.L., Valente, V., Ramachandran, M., Wilson, J.B., Baysal, E., Gu, L-H., and Huisman, T.H.J.: Hemoglobin, 15:487, 1991. 2. Wajcman, H., Kister, J., Vasseur, C., Blouquit, Y., Behnken, J.L., and Galacteros, F.: Blood, 78:206a (Suppl. 1), 1991. Hb Brigham beta100(G2)Pro->Leu CONTACT Internal; central cavity HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.43-0.59 l/l) ELECTROPHORESIS Hb X and Hb A did not separate with standard methodology CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of a mixture of AE-betaX+AE-betaA chains; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCT->CTT at codon 100 FUNCTION STUDIES Increased oxygen affinity; Bohr and 2,3-DPG effects normal STABILITY Normal OCCURRENCE Found in 20 members in four generations of one family OTHER INFORMATION Quantity in the heterozygote not determined REFERENCES 1. Lokich, J.J., Moloney, W.C., Bunn, H.F., Bruckheimer, S.M., and Ranney, H.M.: J. Clin. Invest., 52:2060, 1973. Hb New Mexico beta100(G2)Pro->Arg CONTACT Internal; central cavity HEMATOLOGY Erythrocytosis in the heterozygote who is also heterozygous for Hb S (PCV 0.45-0.51 l/l) ELECTROPHORESIS Hb X migrated between Hb S and Hb C on citrate agar; Hb X moves like Hb S at alkaline pH CHROMATOGRAPHY Attempts to isolate Hb X by DEAE-Sephadex and DEAE-Sephacel chromatography were unsuccessful as Hb X and Hb S migrate close together; Hb X and Hb A separate by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion of betaX+betaA chains; separation of peptides by fingerprinting and by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCT->CGT at codon 100 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; Bohr effect reduced STABILITY Stable OCCURRENCE Found in a 6-year-old Black male but not in his parents OTHER INFORMATION Quantities in the heterozygote: Hb X 53.5%; Hb S 42.2%; Hb A2 4.3% REFERENCES 1. Moo-Penn, W.F., McGuffey, J.E., Jue, D.L., Johnson, M.H., and Schum, T.: Biochim. Biophys. Acta, 832:192, 1985. Hb British Columbia beta101(G3)Glu->Lys CONTACT Internal; central cavity; alpha1beta2 contact HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.49 l/l) ELECTROPHORESIS Hb X moves between Hb A and Hb S at alkaline pH; Hb X moves slightly behind Hb C at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->AAG at codon 101 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in a 26-year-old East Indian male living in Vancouver, BC, Canada OTHER INFORMATION Quantity in the heterozygote 54.1% (starch block electrophoresis) REFERENCES 1. Jones, R.T., Brimhall, B., and Gray, G.: Hemoglobin, 1:171, 1977. 2. Shih, D.T-b., Jones, R.T., Imai, K., and Tyuma, I.: J. Biol. Chem., 260:5919, 1985. Hb Rush beta101(G3)Glu->Gln CONTACT Internal; central cavity; alpha1beta2 contact HEMATOLOGY Mild hemolytic anemia in the heterozygote (PCV 0.35-0.36 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH and at acidic pH; at alkaline pH two zones move between Hb A and Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fin-gerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->CAG at codon 101 FUNCTION STUDIES Normal STABILITY Unstable; forms hybrid Hbs OCCURRENCE Found in three individuals in three generations of a Black family in the USA OTHER INFORMATION Quantity in the heterozygote 35% REFERENCES 1. Adams, J.G., III, Winter, W.P., Tausk, K., and Heller, P.: Blood, 43:261, 1974. 2. Shih, D.T-b., Jones, R.T., Imai, K., and Tyuma, I.: J. Biol. Chem., 260:5919, 1985. Hb Alberta beta101(G3)Glu->Gly CONTACT Internal; central cavity; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.61 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline and acidic pH; at alkaline pH two abnormal bands are observed; one is similar to Hb F, the second moves between Hb A and Hb F; at acidic pH one abnormal band moves between Hb S and Hb C CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography; Hb X elutes as a major abnormal band between Hb A and Hb A2 STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GGG at codon 101 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Normal; forms asymmetric tetramers OCCURRENCE Found in two unrelated Caucasian males from Canada OTHER INFORMATION Quantity in heterozygotes 45% REFERENCES 1. Mant, M.J., Salkie, M.L., Cope, N., Appling, F., Bolch, K., Jayalakshmi, M., Gravely, M., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 1:183, 1977. 2. Stinson, R.A.: J. Lab. Clin. Med., 90:623, 1977. 3. Wong, S.C., Ali, M.A.M., Nicholson, W., Wilson, J.B., Lam, H., and Huisman, T.H.J.: Hemoglobin, 2:557, 1978. Hb Potomac beta101(G3)Glu->Asp CONTACT Internal; central cavity; alpha1beta2 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.55 l/l) ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures CHROMATOGRAPHY No separation obtained on DEAE-Sephadex or Bio-Rex 70 chromatography STRUCTURE STUDIES Tryptic digestion of a mixture of betaX+betaA chains; separation of the peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GAC or GAT at codon 101 FUNCTION STUDIES Increased oxygen affinity; normal 2,3-DPG, Bohr and IHP effects STABILITY Normal OCCURRENCE Found in nine members of a Caucasian family and in an unrelated Caucasian female OTHER INFORMATION Quantity in the heterozygote not provided REFERENCES 1. Charache, S., Jacobson, R., Brimhall, B., Murphy, E.A., Hathaway, P., Winslow, R., Jones, R., Rath, C., and Simkovich, J.: Blood, 51:331, 1978. 2. Rubin, R.N., Ballas, S.K., Burka, E.R., Adachi, K., Asakura, T., and Schwartz, E.: Hemoglobin, 2:447, 1978. Hb Richmond beta102(G4)Asn->Lys CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Normal in the heterozygote (PCV 0.37-0.47 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves in two bands between Hb A and Hb S at alkaline pH, and moves like Hb S at acidic pH CHROMATOGRAPHY Hb X and Hb A are separated by DEAE-Sephadex chromatography, and the betaX and betaA chains by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of tryptic peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->AAA or AAG at codon 102 FUNCTION STUDIES Normal oxygen affinity in red cell lysates; increased oxygen affinity for purified Hb X STABILITY Forms asymmetric hybrids OCCURRENCE Found in several members of Black families, living mainly in Georgia, USA OTHER INFORMATION Quantity in the heterozygote 30-38%; found in combination with Hb S REFERENCES 1. Efremov, G.D., Huisman, T.H.J., Smith, L.L., Wilson,J.B., Kitchens, J.L., Wrightstone, R.N., and Adams, H.R.: J. Biol. Chem., 244:6105, 1969. 2. Greer, J.: J. Mol. Biol., 59:99, 1971. 3. Winslow, R.M. and Charache, S.: J. Biol. Chem., 250:6939, 1975. Hb Kansas beta102(G4)Asn->Thr CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X migrates slightly slower than Hb A (pH 8.4) CHROMATOGRAPHY Hb X and Hb A can be separated by CM-cellulose chromatography; Hb X elutes after Hb A STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->ACC at codon 102 FUNCTION STUDIES Decreased oxygen affinity and cooperativity; normal Bohr effect STABILITY Increased dissociation OCCURRENCE Found in a 14-year-old Caucasian male and his mother OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Reissmann, K.R., Ruth, W.E., and Nomura, T.: J. Clin. Invest., 40:1826, 1961. 2. Bonaventura, J. and Riggs, A.: J. Biol. Chem., 243:9890, 1968. 3. Bunn, H.F.: J. Clin. Invest., 48:126, 1969. 4. Gibson, Q.H., Riggs, A., and Imamura, T.: J. Biol. Chem., 248:5976, 1973. Hb Beth Israel beta102(G4)Asn->Ser CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Cyanosis; normal hematology in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves between Hb F and Hb A CHROMATOGRAPHY Hb X can be isolated by cation exchange chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->AGC at codon 102 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect; decreased cooperativity STABILITY Unstable OCCURRENCE Found in a 13-year-old male of Italian descent but not in his parents; also in a 14-year-old Yugoslavian male but not in his parents OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Nagel, R.L., Lynfield, J., Johnson, J., Landau, L., Bookchin, R.M., and Harris, M.B.: N. Engl. J. Med., 295:125, 1976. 2. Efremov, G.D., Stojmirovic, E., Lam, H.L., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 2:75:1978. 3. Hirsch, R.E. and Nagel, R.L.: J. Biol. Chem., 256:1080, 1981. Hb Saint Mande beta102(G4)Asn->Tyr CONTACT Internal; heme and alpha1beta2 contacts HEMATOLOGY Cyanosis in the heterozygote; normal ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves as Hb F; excellent separation by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->TAC at codon 102 FUNCTION STUDIES Decreased oxygen affinity STABILITY Normal OCCURRENCE Found in a 26-year-old French male and his mother OTHER INFORMATION Quantity in the heterozygote 38% REFERENCES 1. Arous, N., Braconnier, F., Thillet, J., Blouquit, Y., Galacteros, F., Chevrier, M., Bordahandy, C., and Rosa, J.: FEBS Lett., 126:114, 1981. Hb Heathrow beta103(G5)Phe->Leu CONTACT Internal; heme contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.63-0.66 l/l) ELECTROPHORESIS No separation with standard procedures including IEF CHROMATOGRAPHY No separations reported; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; thermolysin; carboxypeptidases A and B; sequencing DNA ANALYSES A TTC->TTG mutation at codon 103 (Ref. 3) FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in members of two English families and in an individual living in Australia OTHER INFORMATION Quantity in the heterozygote 35-45% REFERENCES 1. White, J.M., Szur, L., Gillies, I.D.S., Lorkin, P.A., and Lehmann, H.: Br. Med. J., 3:665:1973. 2. Brennan, S.O., Winterbourn, C.C., and Carrell, R.W.: Hemoglobin, 1:479, 1977. 3. Marsh, G., Marino, G., Pucci, P., Ferranti, P., Malorni, A., Kaeda, J., Marsh, J., and Luzzatto, L.: Hemoglobin 15:43, 1991. Hb Saint Nazaire beta103(G5)Phe->Ile CONTACT Internal; heme contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.505-0.535 l/l) ELECTROPHORESIS No separations by standard methodology; broadening of the Hb A band by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of the peptides by reversed phase HPLC; amino acid analysis; electrospray mass spectral analysis DNA ANALYSES Not reported; presumed mutation TTC->ATC at codon 103 FUNCTION STUDIES Increased oxygen affinity STABILITY Stable OCCURRENCE Found in five subjects in four French families OTHER INFORMATION The increased oxygen affinity of this variant is much less marked than that observed for Hb Heathrow (beta103 Phe->Leu); presumably the introduction of an isoleucyl residue causes less structural modification than that of a leucine residue that results in the loss of contacts between the heme group and globin REFERENCES 1. Wajcman, H., Kister, J., M'Rad, A., Prome, D., Milpied, N., Rapp, M.J., Harousseau, J.L., Riou, J., Bardakdjian, J., and Galacteros, F.: Am. J. Hematol., 44:16, 1993. Hb Camperdown beta104(G6)Arg->Ser CONTACT Central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; excellent separation by IEF; at acidic pH Hb X moves between Hb A and Hb F, close to Hb F CHROMATOGRAPHY Hb X and Hb A separate by DEAE-Sephadex chromatography; the betaX and betaA chains separate by reversed phase HPLC; betaX elutes between betaA and alpha STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing; S. aureus V8 protease treatment; reversed phase HPLC; mass spectrometry DNA ANALYSES Not reported; presumed mutation AGG->AGC or AGT at codon 104 FUNCTION STUDIES Normal; decreased Bohr effect STABILITY Slightly unstable OCCURRENCE Found in members of a Maltese family living in Australia OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Wilkinson, T., Chua, C.G., Carrell, R.W., Robin, H., Exner, T., Lee, K.M., and Kronenberg, H.: Biochim. Biophys. Acta, 393:195, 1975. 2. Kister, J., Barbadjian, J., Blouquit, Y. Bohn, B., Galacteros, F., and Poyart, C.: Hemoglobin, 13:567, 1989. 3. Jensen, O.N. and Roepstorff, P.: Hemoglobin, 15:497, 1991. Hb Sherwood Forest beta104(G6)Arg->Thr CONTACT Central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of the betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGG->ACG at codon 104 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 22-year-old female of Kashmiri Muslim origin OTHER INFORMATION Quantity in the heterozygote 50% REFERENCES 1. Ryrie, D.R., Plowman, D., and Lehmann, H.: FEBS Lett., 83:260, 1977. Hb South Milwaukee beta105(G7)Leu->Phe CONTACT Internal HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation by standard procedures or IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX+betaA chains; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTC->TTC at codon 105 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect; decreased cooperativity STABILITY Normal OCCURRENCE Found in 15 members of a family of English ancestry OTHER INFORMATION Some carriers require phlebotomy to relieve symptoms of chest pain, dizziness, and fatigue REFERENCES 1. Honig, G.R., Vida, L.N., Latorraca, R., and Divgi, A.B.: Am. J. Hematol., 34:199, 1990. Hb Southampton beta106(G8)Leu->Pro ALSO KNOWN AS Casper CONTACT Internal; heme contact HEMATOLOGY Hemolytic anemia in the heterozygote ELECTROPHORESIS No separation with standard procedures; separation with IEF is possible; Hb X focuses at a pI 0.1 unit above that of Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX+betaA chains; separation of peptides by fingerprinting; amino acid analysis; Edman degradation DNA ANALYSES A CTG->CCG mutation at codon 106 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity and Bohr effect STABILITY Unstable OCCURRENCE Found in a 3-year-old English female, in a 10-year-old Caucasian male living in Wyoming, and in a 5-year-old Caucasian male living in Oregon; none of the parents carried the mutation OTHER INFORMATION Quantity in the heterozygotes 15-30% REFERENCES 1. Hyde, R.D., Hall, M.D., Wiltshire, B.G., and Lehmann, H.: The Lancet, ii:1170, 1972. 2. Koler, R.D., Jones, R.T., Bigley, R.H., Litt, M., Lovrien, E., Brooks, R., Lahey, M.E., and Fowler, R.: Am. J. Med., 55:549, 1973. 3. Wajcman, H., Gacon, G., Labie, D., Koler, R.D., and Jones, R.T.: Biochemistry, 14:5017, 1975. 4. Heintz, N.H. and Howard, P.L.: Am. J. Hematol., 30:1, 1989. Hb Tubingen beta106(G8)Leu->Gln CONTACT Internal; heme contact HEMATOLOGY Mild compensated hemolytic anemia in the heterozygote; cyanosis; methemoglobinemia ELECTROPHORESIS No separation with standard procedures in the presence of excess KCN; without KCN a brownish component moves as a smear behind Hb A CHROMATOGRAPHY Hb X elutes between Hb A2 and Hb A on DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC or fingerprinting or cation exchange chromatography; amino acid analysis; Edman sequencing DNA ANALYSES A CTG->CAG mutation at codon 106 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr and 2,3-DPG effects STABILITY Unstable OCCURRENCE Found in two members of a German family and also in a middle-aged Belgian female OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Kleihauer, E., Waller, H.D., Benohr, H.Chr., Kohne, E., and Gelinsky, P.: Klin. Wschr., 48:651, 1971. 2. Kohne, E., Kley, H.P. Kleihauer, E., Versmold, H., Benohr, H.Ch., and Braunitzer, G.: FEBS Lett., 64:443, 1976. 3. Philippe, M., Larondelle, Y., Vaerman, J.L., Martiat, Ph., Galacteros, F., Wajcman, H., and Lambert, M.: Hemoglobin, 17:373, 1993. Hb Terre Haute beta106(G8)Leu->Arg CONTACT Internal; heme contact HEMATOLOGY Anemia in the heterozygote IDENTIFICATION Hb X was identified through sequence analysis of the PCR product of DNA isolated from a 10-year-old microscopic slide. Sequence was limited to the third exon; codon 112 was normal (TGT for cysteine) but a T->G mutation was observed at codon 106 (CTG->CGG) FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in two (deceased) persons OTHER INFORMATION Previously identified as Hb Indianapolis [beta112(G14)Cys-> Arg]; the error was corrected in this abstract. For further details see beta112-Hb Indianapolis REFERENCES 1. Coleman, M.B., Steinberg, M.H., and Adams, J.G., III: Blood, 76:57a (Suppl. 1), 1990. 2. Coleman, M.B., Steinberg, M.H., and Adams, J.G., Ill: J. Biol. Chem., 266:5798, 1991. 3. Girodonm, E., Ghanem, N., Vidaud, M., Riou, J., Martin, J., Galacteros, F., and Goossens, M.: Ann. Hematol., 65:188, 1992. Hb Burke beta107(G9)Gly->Arg CONTACT Internal HEMATOLOGY Hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH (migrates between Hb S and Hb A) and at acid pH (moves approximately with Hb S) CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC at codon 107 FUNCTION STUDIES Decreased oxygen affinity and cooperativity; increased Bohr effect STABILITY Unstable OCCURRENCE Found in two members of a Caucasian family OTHER INFORMATION Quantity in the heterozygote 30% REFERENCES 1. Turner, J.W., Jr., Jones, R.T., Brimhall, B., DuVal, M.C., and Koler, R.D.: Biochem. Genet., 14:577, 1976. Hb Lulu Island beta107(G9)Gly->Asp CONTACT Internal HEMATOLOGY Not available ELECTROPHORESIS Hb X focuses slightly ahead of Hb A (IEF) CHROMATOGRAPHY Hb X and Hb A partially separate by cation exchange HPLC; the betaX and betaA chains separate on a reversed phase HPLC column (elution order: betaX, betaA, delta, alpha) STRUCTURE STUDIES Not done DNA ANALYSES A GGC->GAC mutation at codon 107 FUNCTION STUDIES Normal oxygen affinity STABILITY Unstable OCCURRENCE Found in an East Indian female OTHER INFORMATION The only carrier is compound heterozygous for Hb X and betao-thal (codon 15, TGG->TAG) REFERENCES 1. Gray, G.R., Manson, H.E., Gu, L-H., Leonova, J.Ye., and Huisman, T.H.J.: Am. J. Hematol., 50:26, 1995. Hb Yoshizuka beta108(G10)Asn->Asp CONTACT Central cavity; alpha1beta1 contact HEMATOLOGY Slight anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X can be separated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAC->GAC at codon 108 FUNCTION STUDIES Decreased oxygen affinity; normal cooperativity STABILITY Stable OCCURRENCE Found in several members of a Japanese family OTHER INFORMATION Quantity in heterozygotes ~50% REFERENCES 1. Imamura, T., Fujita, S., Ohta, Y., Hanada, M., and Yanase, T.: J. Clin. Invest., 48: 2341, 1969. Hb Presbyterian beta108(G10)Asn->Lys CONTACT Central cavity; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated by standard procedures; Hb X moves between Hb A and Hb F at alkaline pH and moves to the position of Hb C at acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAC->AAA or AAG at codon 108 FUNCTION STUDIES Decreased oxygen affinity STABILITY Normal OCCURRENCE Found in members of a family in the USA; in a German family, and a Spanish family OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Moo-Penn, W.F., Wolff, J.A., Simon, G., Vacek, M., Jue, D.L., and Johnson, M.H.: FEBS Lett., 92:53, 1978. 2. Kohne, E., Behnken, L.J., Leupold, D., Rogge, H., Martin, H., and Kleihauer, E.: Hemoglobin, 3:365, 1979. 3. Horst, J., Oehme, R., Kleihauer, E., and Kohne, E.: Hum. Genet., 64:263, 1983. 4. Villegas, A., Wilson, J.B., Chen, S.S., Calero, F., Reinares, L., Huisman, T.H.J., and Espinos, D.: Acta Haematol., 76:161, 1986. Hb San Diego beta109(G11)Val->Met CONTACT Internal HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.62 l/l) ELECTROPHORESIS No separation of Hb X and Hb A CHROMATOGRAPHY No separation of Hb X and Hb A STRUCTURE STUDIES Tryptic digestion of AE-betaX (or betaX+betaA) chains; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GTG->ATG mutation at codon 109 (Ref. 5) FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect; decreased cooperativity STABILITY Normal OCCURRENCE Found in a Filipino family living in the USA, in an Anglo-Saxon family in England, in a Japanese family, and in a West Indian family OTHER INFORMATION Quantity in the heterozygotes not provided; occurred in combination with Hb S (Ref. 5) REFERENCES 1. Nute, P.E., Stamatoyannopoulos, G., Hermodson, M.A., and Roth, D.: J. Clin. Invest., 53:320, 1974. 2. Anderson, N.L.: J. Clin. Invest., 53:329, 1974. 3. Chanarin, I., Samson, D., Lang, A., Casey, R., Lorkin, P.A., and Lehmann, H.: Br. J. Haematol., 30:167, 1975. 4. Nakatsuji, T., Wilson, J.B., Lam, H., and Huisman, T.H.J.: J. Chromatogr., 259: 511, 1983. 5. Williamson, D., Perry, D.J., Brown, K., Langdown, J.V., and de Silva, C.: Hemoglobin, 19:27, 1995. Hb Johnstown beta109(G11)Val->Leu CONTACT Internal HEMATOLOGY Mild erythrocytosis (PCV 0.52-.053 l/l) ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures CHROMATOGRAPHY No separation of Hb X and Hb A; betaX and betaA separate by reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES The betaX chain was isolated by reversed phase HPLC, oxidized, digested with trypsin, and the tryptic peptides separated by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTG->CTG at codon 109 FUNCTION STUDIES Increased oxygen affinity STABILITY Not reported OCCURRENCE Found in three members of a Caucasian family OTHER INFORMATION Quantity in the heterozygote about 50% (by reversed phase HPLC) REFERENCES 1. Jones, R.T., Saiontz, H.I., Head, C., Shih, D.T.B., and Fairbanks, V.F.: Hemoglobin, 14:147, 1990. Hb Showa-Yakushiji beta110(G12)Leu->Pro CONTACT Internal HEMATOLOGY Hemolytic anemia with hypochromia and microcytosis; reticulocytosis ELECTROPHORESIS No separations reported CHROMATOGRAPHY No separations reported STRUCTURE STUDIES Not reported; Hb X could not be isolated DNA ANALYSES DNA analyses revealed that leucine (CTG) at codon 110 was replaced by proline (CCG); this mutation was confirmed by restriction analysis because it created a new recognition site for the Msp I enzyme (CTGG->CCGG) FUNCTION STUDIES Not reported STABILITY Negative OCCURRENCE Found in a 55-year-old Japanese female OTHER INFORMATION beta-Thalassemic phenotype REFERENCES 1. Kobayashi, Y., Fukumaki, Y., Komatsu, N., Ohba, Y., Miyaji, T., and Miura, Y.: Blood, 70:1688, 1987. 2. Naritomi, Y., Naito, Y., Nakashima, H., Yokota, E., and Imamura, T.: Hum. Genet., 80:11, 1988. Hb Peterborough beta111(G13)Val->Phe CONTACT Internal HEMATOLOGY Mild anemia in the heterozygote; reticulocytosis ELECTROPHORESIS No separation reported using standard techniques CHROMATOGRAPHY No separation of Hb X and Hb A reported; the variant was obtained from a blood sample of a subject who was also heterozygous for Hb Lepore STRUCTURE STUDIES Tryptic digestion of AE-globin; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTC->TTC at codon 111 FUNCTION STUDIES Decreased oxygen affinity; normal Bohr effect and cooperativity STABILITY Unstable OCCURRENCE Found in a few members of an Italian family living in England OTHER INFORMATION The son is heterozygous for Hb X (33.4%) and Hb Lepore REFERENCES 1. King, M.A.R., Wiltshire, B.G., Lehmann, H., and Morimoto, H.: Br. J. Haematol., 22:125, 1972. Hb Stanmore beta111(G13)Val->Ala CONTACT Internal; alpha1beta1 contact HEMATOLOGY No data available for the simple heterozygote; the proband is compound heterozygous for Hb X and a beta-thal (Hb 8.5 g/dl) ELECTROPHORESIS No separations observed CHROMATOGRAPHY No separations observed; reversed phase HPLC showed no betaA chain but a betaX chain was eluted in the normal pre-beta position STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTC->GCC at codon 111 FUNCTION STUDIES Decreased oxygen affinity STABILITY Unstable OCCURRENCE Found in a 20-year-old female of Italian descent OTHER INFORMATION The parents did not carry the variant but were heterozygous for a beta-thal; non-paternity was not excluded REFERENCES 1. Como, P.F., Wylie, B.R., Trent, R.J., Bruce, D., Volpato, F., Wilkinson, T., Kronenberg, H., Holland, R.A.B., and Tibben, E.A.: Hemoglobin, 15:53, 1991. Hb Indianapolis beta112(G14)Cys->Arg CONTACT Internal; central cavity; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote; reticulocytosis ELECTROPHORESIS Hb X moves slower than Hb A in IEF CHROMATOGRAPHY Not reported; the betaX, betaA, and alpha chains can be separated on a CM-cellulose column (the Clegg procedure) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC or fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGT->CGT at codon 112 FUNCTION STUDIES Not determined STABILITY Unstable OCCURRENCE In several members of a Spanish family OTHER INFORMATION 1) Quantity in the heterozygote was determined by scanning of the strip revealing the separation of the betaX, betaA, and alpha chains; it was found to be 38-40% betaX and 60-62% betaA. 2) The beta112 Cys->Arg replacement was originally assigned to an abnormal Hb in two members of an European family. Both persons had severe hemolytic anemia with reticulocytosis and were splenectomized. The Hb variant was found to be extremely unstable and its identity could only be studied by biosynthetic analysis in which a radio-active abnormal peak was observed. Unfortunately, the identification of this fraction was incorrect; instead of a Cys->Arg replacement at beta112 as originally observed, a beta106 Leu->Arg change was found in subsequent DNA analysis. The variant was renamed Hb Terre Haute (Ref. 4). REFERENCES 1. Adams, J.G., III, Boxer, L.A., Baehner, R.L., Forget, B.G., Tsistrakis, G.A., and Stein-berg, M.H.: J. Clin. Invest., 63:931, 1979. 2. Adams, J.G., Steinberg, M.H., Boxer, L.A., Baehner, R.L., Forget, B.G., Tsistrakis, G.A.: J. Biol. Chem., 254:3479, 1979. 3. Baiget, M., Gomez Pereira, C., Jue, D.l., Johnson, M.h., McGuffey, J.E., and Moo-Penn, W.F.: Hemoglobin, 10:483, 1986 4. Coleman, M.B., Steinberg, M.H., and Adams, J.G., III: Blood, 76:57a (Suppl. 1), 1990. Hb Yahata beta112(G14)Cys->Tyr CONTACT Internal; central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated by IEF; Hb X moves ahead of Hb A CHROMATOGRAPHY Hb X moves slightly faster than Hb A by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES A TGT->TAT mutation at codon 112 FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 27-year-old Japanese male OTHER INFORMATION Quantity in the heterozygote 45% REFERENCES 1. Harano, T., Harano, K., Kushida, Y., and Ueda, S.: Hemoglobin, 15:109, 1991. Hb New York beta113(G15)Val->Glu ALSO KNOWN AS Kaohsiung CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A; no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A readily separate by cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting and HPLC; amino acid analysis; sequencing DNA ANALYSES A GTG->GAG mutation at codon 113 (Ref. 6) FUNCTION STUDIES Decreased oxygen affinity and Bohr effect; normal cooperativity STABILITY Slightly unstable OCCURRENCE Found in many Chinese families OTHER INFORMATION Quantity in the heterozygote 40-45%; found in combination with Hb E, with alpha-thal, and with betao-thal REFERENCES 1. Ranney, H.M., Jacobs, A.S., and Nagel, R.L.: Nature, 213:876, 1967. 2. Pootrakul, S., Wasi, P., Na-Nakorn, S., and Dixon, G.H.: J. Med. Assoc. Thai., 54:688, 1971. 3. Todd, D., Chan, V., Schneider, R.G., Dozy, A.M., Kan, Y.W., and Chan, T.K.: Br. J. Haematol., 46:557, 1980. 4. Sugihara, J., Imamura, T., Imoto, T., and Yanase, T.: Biochim. Biophys. Acta, 669:105, 1981. 5. Zeng, Y-T. and Huang, S-Z.: Hemoglobin, 6:61, 1982. 6. Chang, J-G., Lee, L-S., Chen, P-H., and Chen, Y-H.: Hemoglobin, 16:123, 1992. Hb Zengcheng beta114(G16)Leu->Met CONTACT Internal HEMATOLOGY Normal in the newborn ELECTROPHORESIS IEF detected a slightly faster moving beta chain variant CHROMATOGRAPHY The betaX and betaA chains can be separated by reversed phase HPLC STRUCTURE STUDIES The betaX chain was aminoethylated, digested with trypsin, and the resulting peptides separated by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CTG->ATG at codon 114 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Discovered in a Chinese baby from Zengcheng, PR China; parents were not available for study OTHER INFORMATION None REFERENCES 1. Plaseska, D., Wilson, J.B., Gu, L-H., Kutlar, F., Huisman, T.H.J., Zeng, Y-T., and Shen, M.: Hemoglobin, 14:555, 1990. Hb Durham-N.C. beta114(G16)Leu->Pro ALSO KNOWN AS Brescia CONTACT Internal HEMATOLOGY Moderate anemia in the heterozygote ELECTROPHORESIS Not reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES A CTG->CCG mutation at codon 114 FUNCTION STUDIES Not reported STABILITY Not reported; presumably very unstable OCCURRENCE Found in a 29-year-old female of Irish descent, in an Italian family, and in members of two Russian families OTHER INFORMATION This is another thalassemic Hb; slightly elevated Hb A2 and Hb F levels in the heterozygote REFERENCES 1. deCastro, C.M., Lee, M., Fleenor, D.E., Devlin, B., and Kaufman, R.E.: Blood, 80:6a (Suppl. 1), 1992. 2. Murru, S.: Personal communication, 1992. 3. Curuk, M.A., Molchanova, T.P., Postnikov, Yu.V., Pobedimskaya, D.D., Liang, R., Baysal, E., Kolodey, S., Smetanina, N.S., Tokarev, Yu.N., Rumyantsev, A.G., and Huisman,T.H.J.: Am. J. Hematol., 46:329, 1994. Hb Madrid beta115(G17)Ala->Pro CONTACT Internal; alpha1beta1 contact HEMATOLOGY Moderately severe hemolytic anemia in the heterozygote ELECTROPHORESIS No separation observed with any technique CHROMATOGRAPHY Hb X and Hb A separate by cation exchange HPLC; excellent separation of chains by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion; separation of the peptides by reversed phase HPLC; fingerprinting; amino acid analysis; sequencing DNA ANALYSES A GCC->CCC mutation at codon 115 (Ref. 2) FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 16-year-old male of Spanish origin (not in parents or siblings), and in a Black family OTHER INFORMATION Quantity in heterozygotes ~13% REFERENCES 1. Outeirino, J., Casey, R., White, J.M., and Lehmann, H.: Acta Haematol., 52:53, 1974. 2. Molchanova, T.P., Postnikov, Yu.V., Wilson, J.B., Webber, B.B., Gu, L-H., Sabio, H., Waldron, P., and Huisman, T.H.J.: Hemoglobin, 17:251, 1993. Hb Hradec Kralove (or HK) beta115(G17)Ala->Asp CONTACT Internal; alpha1beta1 contact HEMATOLOGY Moderate hemolytic anemia in the heterozygote; reticulocytosis ELECTROPHORESIS Hb X was not detected by any standard technique or by IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES A GCC->GAC mutation at codon 115 FUNCTION STUDIES Not reported STABILITY Very unstable OCCURRENCE Found in a 32-year-old Czech woman and her daughter OTHER INFORMATION This is a thalassemic Hb that is most difficult to detect except by DNA sequencing REFERENCES 1. Divoky, V., Svobodova, M., Indrak, K., Chrobak, L., Molchanova, T.P., and Huisman, T.H.J.: Hemoglobin, 17:319, 1993. Hb Hafnia beta116(G18)His->Gln CONTACT External; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Complete separation is obtained by IEF; Hb X focuses ahead of Hb A CHROMATOGRAPHY Not reported; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion of oxidized betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAT->CAA or CAG at codon 116 FUNCTION STUDIES Marginally increased oxygen affinity STABILITY Normal OCCURRENCE Found in six members of a Danish family OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Blanke, S., Johnsen, A., Wimberley, P.D., and Mortensen, H.B.: Biochim. Biophys. Acta, 955:214, 1988. Hb P-Galveston beta117(G19)His->Arg CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves in the position of Hb S) but not at acidic pH CHROMATOGRAPHY Hb X and Hb A can be separated by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC at codon 117 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in several Black families OTHER INFORMATION Quantity in heterozygotes 45-50%; found in combination with Hb S, with Hb C, and with beta-thal REFERENCES 1. Dherte, P., Lehmann, H., and Vandepitte, J.: Nature, 184:1133, 1959. 2. Silvestroni, E., Bianco, I., and Brancati, C.: Nature, 191:292, 1961. 3. Schneider, R.G., Alperin, J.B., Brimhall, B., and Jones, R.T.: J. Lab. Clin. Med., 73:616, 1969. 4. Di Iorio, E.E., Winterhalter, K.H., Wilson, K., Rosenmund, A., and Marti, H.R.: Blut, 31:61, 1975. 5. Huisman, T.H.J.: FEBS Lett., 94:68, 1978. Hb Saitama beta117(G19)His->Pro CONTACT External HEMATOLOGY Unstable Hb hemolytic anemia in the heterozygote ELECTROPHORESIS No separation reported CHROMATOGRAPHY No separation reported STRUCTURE STUDIES Hb X isolated by pCMB; alpha and beta chains separated by CM-cellulose chromatography; tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CCC at codon 117 FUNCTION STUDIES Decreased oxygen affinity; increased 2,3-DPG level STABILITY Unstable OCCURRENCE Found in a 23-year-old Japanese female, but not in her parents or other members of her family OTHER INFORMATION Quantity in the heterozygote not reported REFERENCES 1. Ohba, Y., Hasegawa, Y., Amino, H., Miwa, S., Nakatsuji, T., Hattori, Y., and Miyaji, T.: Hemoglobin, 7:47, 1983. Hb Minneapolis-Laos beta118(GH1)Phe->Tyr CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS IEF revealed an extra band with a mobility like Hb F CHROMATOGRAPHY Hb X and Hb A can be separated on a DEAE-cellulose or a DEAE-Sephadex column STRUCTURE STUDIES After aminoethylation, the betaX was digested with trypsin and the resulting fragments separated by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation TTT->TAT at codon 118 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 27-year-old Laotian male and a 1-year-old Cambodian male and his mother OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Hedlund, B., Paine, S., Smith, C.M., II, Raines, J., Morrison, W.T., and Adams, J., III: Hemoglobin, 8:75, 1984. 2. Kleman, K., Lubin, B., Kutlar, A., Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 11:401, 1987. Hb Fannin-Lubbock beta119(GH2)Gly->Asp CONTACT External; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X and Hb A separate on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion of AE-beta chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES In a recent paper (Ref. 3) five Spanish families with Hb Fannin-Lubbock are described; in all instances two nucleotide changes were observed: GGC->GAC at codon 119 (Gly->Asp) and GTC->CTG at codon 111 (Val->Leu) FUNCTION STUDIES Normal STABILITY Unstable OCCURRENCE Found in members of two Mexican-American families, and in five Spanish families OTHER INFORMATION Quantity in heterozygotes 45-50% REFERENCES 1. Moo-Penn, W.F., Bechtel, K.C., Johnson, M.H., Jue, D.L., Therrell, B.L., Jr., Morrison, B.Y., and Schmidt, R.M.: Biochim. Biophys. Acta, 453:472, 1976. 2. Schneider, R.G., Berkman, N.L., Brimhall, B., and Jones, R.T.: Biochim. Biophys. Acta, 453:478, 1976. 3. Qin, W-B., Pobedimskaya, D.D., Molchanova, T.P., Wilson, J.B., Gu, L-H., de Pablos, J.Ma., and Huisman, T.H.J.: Hemoglobin, 18:297, 1994. Hb Bougardirey-Mali beta119(GH2)Gly->Val CONTACT External; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures; Hb X moves like Hb F in IEF on polyacrylamide gel CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting and by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGC->GTC at codon 119 FUNCTION STUDIES Normal oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in a 32-year-old African male from Mali OTHER INFORMATION Quantity in the heterozygote 35% REFERENCES 1. Chen-Marotel, J., Braconnier, F., Blouquit, Y., Martin-Caburi, J., Kammerer, J., and Rosa, J.: Hemoglobin, 3:253, 1979. Hb Iowa beta119(GH2)Gly->Ala CONTACT External; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate by IEF; Hb X has the position near Hb F CHROMATOGRAPHY No separation of Hb X and Hb A by cation exchange HPLC; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->GCC at codon 119 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 9-month-old infant and her mother OTHER INFORMATION The proband was also heterozygous for Hb S REFERENCES 1. Plaseska, D., de Alarcon, P.A., McMillan, S., Walbrecht, M., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 14:432, 1990. Hb Hijiyama beta120(GH3)Lys->Glu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X is fast moving CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of the peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAA->GAA at codon 120 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in the mother and son of a Japanese family, and a diabetic Finnish boy OTHER INFORMATION Quantity in the heterozygote 58% REFERENCES 1. Miyaji, T., Oba, Y., Yamamoto, K., Shibata, S., Iuchi, I., and Hamilton, H.B.: Science, 159:204, 1968. 2. Puukka, R., Hekali, R., Akerblom, H.K., Kaar, M-L., Dukes, M., and Lehmann, H.: Clin. Chim. Acta, 121:51, 1982. Hb Riyadh beta120(GH3)Lys->Asn ALSO KNOWN AS Karatsu CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH (Hb X moves faster); no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of the peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAA->AAC or AAT at codon 120 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in members of a few Saudi Arabian families, in a family of Mexican-Spanish ancestry, in members of an Asian Indian family, and in an 82-year-old Japanese male OTHER INFORMATION Quantity in the heterozygote 50-54%; found in combination with alpha- and betao-thal REFERENCES 1. El-Hazmi, M.A.F. and Lehmann, H.: Hemoglobin, 1:59, 1976. 2. Budge, L.J., Bradley, T.B., and Graham, J.L.: Hemoglobin, 1:283, 1977. 3. Miyaji, T., Ohba, Y., Matsuoka, M., Kudoh, H., Asano, M., Yamamoto, K., and Satoh, T.: Hemoglobin 1:462, 1977. 4. Pinkerton, P.H., Wilson, J.B., Lam, H., Williams, D., and Huisman, T.H.J.: Hemoglobin, 3:451, 1979. 5. Hidaka, K. and Iuchi, I.: Kawasaki Med. J., 12:149, 1986. Hb Takamatsu beta120(GH3)Lys->Gln CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAA->CAA at codon 120 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in three unrelated Japanese families OTHER INFORMATION Quantity in the heterozygote 48% REFERENCES 1. Iuchi, I., Hidaka, K., Harano, T., Ueda, S., Shibata, S., Shimasaki, S., Mizushima, J., Kubo, N., Miyake, T., and Uchida, T.: Hemoglobin, 4:165, 1980. Hb Jianghua beta120(GH3)Lys->Ile CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAA->ATA at codon 120 FUNCTION STUDIES Not reported STABILITY Normal or mildly unstable OCCURRENCE Found in members of a Chinese family of the Han ethnic group OTHER INFORMATION Quantity in the heterozygote 50.1% REFERENCES 1. Lu, Y-Q, Fan, J-L., Liu, J-F., Hu, H-L., Peng, X-H., Huang, C-H., Huang, P-Y., Chen, S-S., Jia, P-C., Yang, K-G., Liang, C-C., Ren, X-D., and Zuo, C-R.: Hemoglobin, 7: 321, 1983. Hb D-Los Angeles beta121(GH4)Glu->Gln ALSO KNOWN AS D-Punjab; D-North Carolina; D-Portugal; Oak Ridge; D-Chicago CONTACT External HEMATOLOGY Normal in heterozygotes and homozygotes ELECTROPHORESIS Hb X moves slower (like Hb S) than Hb A at alkaline pH; no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by both cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or cation exchange chromatography or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAA->CAA mutation at codon 121 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Hb D-Los Angeles is primarily found in Northern India but is wide-spread and has been observed in persons from China, England, Holland, Australia, Greece, Yugoslavia, Turkey, etc. It is the fourth most frequently occurring Hb variant OTHER INFORMATION Quantity in the heterozygote ~40%; it has been found in combination with Hb S, Hb C, Hb E, beta-thal, alpha-thal, and in the homozygous state REFERENCES 1. Itano, H.: Proc. Natl. Acad. Sci. USA, 37:775, 1951. 2. Hynes, M. and Lehmann, H.: Br. Med. J., 2:923, 1956. 3. Baglioni, C.: Biochim. Biophys. Acta, 59:437, 1969. 4. Bunn, H.F. and Forget, B.G.: Hemoglobin: Molecular, Genetic and Clinical Aspects, W.B. Saunders Company, Philadelphia, 1986. 5. Huisman, T.H.J., editor: The Hemoglobinopathies, Methods in Hematology, Vol. 15, Churchill Livingstone, Edinburgh, 1986. 6. Weatherall, D.J. and Clegg, J.B., editors: The Haemoglobinopathies, Bailliere's Clinical Haematology, Vol. 6, W.B. Saunders Company, London, 1993. Hb O-Arab beta121(GH4)Glu->Lys ALSO KNOWN AS Egypt CONTACT External HEMATOLOGY Normal in heterozygotes; mild anemia in homozygotes ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves about like Hb C; at acid pH Hb X moves close to Hb A CHROMATOGRAPHY Hb X and Hb A can readily be separated by anion and cation exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC, fingerprinting, cation exchange chromatography or reversed phase HPLC; amino acid analysis DNA ANALYSES A GAA->AAA mutation at codon 121 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found mainly in Gypsies and in Pomaks (a population group in the Balkan countries) and also in Arabian, Egyptian, and Black families OTHER INFORMATION Quantity in the heterozygote 30-40%; found in combination with Hb S, Hb C, beta-thal, and alpha-thal; found in the homozygous condition in Bulgaria and Yugoslavia REFERENCES 1. Baglioni, C. and Lehmann, H.: Nature, 196:229, 1962. 2. Vella, F., Beale, D., and Lehmann, H.; Nature, 209:308, 1966. 3. Milner, P.F., Miller, C., Grey, R., Seakins, M., De Jong, W.W., and Went, L.N.: N. Engl. J. Med., 283:1417, 1970. 4. Efremov, G., Apostolova, S., Duma, K., Wilson, J.B., and Huisman, T.H.J.: Acta Med. Iug., 37:359, 1973. 5. Kantchev, K.N., Tcholakov, B.N., Casey, R., Lehmann, H., and El Hazmi, M.: Humangenetik, 26: 93, 1975. 6. Efremov, G.D., Sadikario, A., Stojancov, A., Dojcinov, D., and Huisman, T.H.J.: Hemoglobin, 1:389, 1977. Hb St. Francis beta121(GH4)Glu->Gly CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb S or Hb D-Los Angeles CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequence analysis DNA ANALYSES Not reported; presumed mutation GAA->GGA at codon 121 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 60-year-old Caucasian female OTHER INFORMATION Quantity in the heterozygote 39% REFERENCES 1. Abourzik, N.N., Conlon, M., Zordon, G., Hine, T.K., Johnson, M.H., Jue, D.L., and Moo-Penn, W.F.: Hemoglobin, 15:115, 1991. Hb Beograd beta121(GH4)Glu->Val ALSO KNOWN AS D-Camperdown CONTACT External HEMATOLOGY Normal in heterozygotes ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb S; no separation at acidic pH CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography, reversed phase HPLC, or fingerprinting; amino acid analysis; sequencing DNA ANALYSES A GAA->GTA mutation at codon 121 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in members of several Yugoslavian families and in a Turkish family OTHER INFORMATION Quantity in heterozygotes 26-38%; found in combination with beta-thal and with Hb Strumica [alpha112(G19)His->Arg] REFERENCES 1. Efremov, G.D., Duma, H., Rudivic, R., Rolovic, Z., Wilson, J.B., and Huisman, T.H.J.: Biochim. Biophys. Acta, 328:81, 1973. 2. Wilkinson, T., Gough, P., Owen, M.C., Carrell, R.W., and Kronenberg, H.: Med. J. Austrl., 2:636, 1974. 3. Rudivic, R., Efremov, G.D., Juricic, D., Rolovic, A., Ruzdic, I., and Pendix, S.: Acta Haematol., 54:180, 1975. 4. Wilkinson, T., Carrell, R.W., Brennan, S., Gough, P., Robin, H., and Kronenberg, H.: Pathology, 9:27, 1977. 5. Aksoy, M., Kutlar, A., Dincol, G., Erdem, S., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 8:417, 1984. Hb D-Neath beta121(GH4)Glu->Ala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves like Hb S CHROMATOGRAPHY Hb X was isolated by DEAE-Sephacel chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAA->GCA at codon 121 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in members of a Caucasian family in England OTHER INFORMATION Quantity in the heterozygote 36% REFERENCES 1. Welch, S.G. and Bateman, C.: Hemoglobin, 17:255, 1993. Hb Villejuif beta123(H1)Thr->Ile CONTACT External; alpha1beta1 contact HEMATOLOGY Probably normal in the heterozygote; the only known carrier had a coincidental polycythemia vera ELECTROPHORESIS Hb X and Hb A do not separate at alkaline pH; an abnormal band, close to Hb A, was observed by IEF CHROMATOGRAPHY No separation reported; the betaX and betaA chains can be separated by reversed phase HPLC (see reference for techniques) STRUCTURE STUDIES Tryptic digest of partially purified betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation ACC->ATC at codon 123 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in an 87-year-old woman of French extraction OTHER INFORMATION Quantity in the heterozygote not determined REFERENCES 1. Wajcman, H., Mrad, A., Blouquit, Y., Parmentier, C., Riou, J., and Galacteros, F.: Am. J. Hematol., 32:294, 1989. Hb Khartoum beta124(H2)Pro->Arg CONTACT External; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb S CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of the AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CCA->CGA at codon 124 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a male from Khartoum; family was not available for study OTHER INFORMATION Quantity in the heterozygote 30% REFERENCES 1. Clegg, J.B., Weatherall, D.J., Wong, H.B., and Mustafa, D.: Nature, 22:379, 1969. Hb Ty Gard beta124(H2)Pro->Gln CONTACT External; alpha1beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.43-0.54 l/l) ELECTROPHORESIS No separation of Hb X and Hb A by conventional methods; Hb X moves ahead of Hb A in IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain (obtained by pCMB precipitation); separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CCA->CAA at codon 124 FUNCTION STUDIES Increased oxygen affinity; normal cooperativity and Bohr effect STABILITY Normal OCCURRENCE Found in father and daughter living in France OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Bursaux, E., Blouquit, Y., Poyart, C., Rosa, J., Arous, N., and Bohn, B.: FEBS Lett., 88:155, 1978. Hb Tunis beta124(H2)Pro->Ser CONTACT External; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation by conventional techniques; in IEF Hb X moves just ahead of Hb A CHROMATOGRAPHY No separation reported; the betaX and betaA chains separate in reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of tryptic peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CCA->TCA at codon 124 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in members of a Tunisian family OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Mrad, A., Blouquit, Y., Lacombe, C., Blibech, R., Arous, N., Bardakdjian, J., Kastally, R., Rosa, J., and Galacteros, F.: Hemoglobin, 12:23, 1988. Hb Hofu beta126(H4)Val->Glu CONTACT External HEMATOLOGY Normal or mild anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose or DEAE-Sephadex chromatography; partial separation by cation exchange HPLC; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis DNA ANALYSES A GTG->GAG mutation at codon 126 (Ref. 5) FUNCTION STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in Japanese, Indian, Black, and Spanish families OTHER INFORMATION Quantity in the heterozygote 28-31%; found in combination with Hb S and with betao-thal REFERENCES 1. Miyaji, T., Ohba, Y., Yamamoto, K., Shibata, S., Iuchi, I., and Takenaka, H.: Nature, 217:89, 1968. 2. Brittenham, G., Lozoff, B., Harris, J.W., Nayudu, N.V.S., Gravely, M., Wilson, J.B., Lam, H., and Huisman, T.H.J.: Hemoglobin, 2:541, 1978. 3. Russo, F.M., John, M.E., Walterman, M.R., Simon, L.M., and Sheehan, R.G.: Hemoglobin, 3:83, 1979. 4. Arends, T., Garlin, G., Guevara I., J.M., Amesty, C., Perez-Bandez, O., Lorkin, P.A., Lehmann, H., and Castillo, O.: Acta Haematol., 73:51, 1985. 5. Pande, P.L., Prakash, S., Tiwary, R.S., Kazanetz, E.G., Leonova, J.Ye., and Huisman, T.H.J.: Hemoglobin, 19:301, 1995. Hb Beirut beta126(H4)Val->Ala CONTACT External HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A with conventional techniques or with IEF CHROMATOGRAPHY No separation of Hb X and Hb A by cation or anion exchange HPLC; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GTG->GCG at codon 126 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in members of a Lebanese family OTHER INFORMATION Quantity in the heterozygote 42-46% REFERENCES 1. Strahler, J.R., Rosenbloom, B.B., and Hanash, S.M.: Science, 221:869, 1983. Hb Dhonburi beta126(H4)Val->Gly ALSO KNOWN AS Neapolis CONTACT External HEMATOLOGY Mild anemia in the heterozygote; microcytosis and hypochromia ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures; partial separation of Hb X and Hb A by IEF CHROMATOGRAPHY No separation reported; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES A GTG->GGG mutation at codon 126 (Ref. 3) FUNCTION STUDIES Probably normal STABILITY Unstable OCCURRENCE Found in a Thai family, three Italian families, and a few German families OTHER INFORMATION Quantity in the heterozygote is ~30%; thalassemic features REFERENCES 1. Bardakdjian-Michau, J., Fucharoen, S., Delanoe-Garin, J., Kister, J., Lacombe, C., Winichagoon, P., Blouquit, Y., Riou, J., Wasi, P., and Galacteros, F.: Am. J. Hematol., 35:96, 1990. 2. Pagano, L., Lacerra, G., Carmadella, L., De Angioletti, M., Fioretti, G., Maglione, G., de Bonis, C., Guarino, E., Viola, A., Cutolo, R., De Rosa, L., and Carestia, C.: Blood, 78: 3070, 1991. 3. Divoky, V., Bisse, E., Wilson, J.B., Gu, L-H., Wieland, H., Heinrichs, I., Prior, J.F., and Huisman, T.H.J.: Biochim. Biophys. Acta, 1180:173, 1992. Hb Complutense beta127(H5)Gln->Glu CONTACT alpha1beta1 contact HEMATOLOGY Mild anemia in the heterozygote ELECTROPHORESIS No separation with standard techniques CHROMATOGRAPHY No separation by cation and anion exchange HPLC; betaX separates from betaA by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAG->GAG at codon 127 FUNCTION STUDIES Not reported STABILITY Mildly unstable OCCURRENCE Found in a few Spanish families OTHER INFORMATION The Gln->Glu replacement at beta127 was first thought to be the abnormality in a Turkish family (Ref. 1); this erroneous characterization was corrected in 1986; the Turkish abnormality was renamed Hb J-Antakya with a beta65(E9)Lys->Met replacement (Ref. 2) REFERENCES 1. Altay, C., Altinoz, N., Wilson, J.B., Bolch, K.C., and Huisman, T.H.J.: Biochim. Biophys. Acta, 434:1, 1976. 2. Huisman, T.H.J., Wilson, J.B., Kutlar, A., Yang, K-G., Chen, S-S., Webber, B., Altay, C., and Villegas Martinez, A.: Biochim. Biophys. Acta, 871:229, 1986. 3. Villegas, A., Espinos, D., Calero, F., and Huisman, T.H.J.: Sangre, 32:382, 1987. Hb Brest beta127(H5)Gln->Lys CONTACT alpha1beta1 contact HEMATOLOGY Hemolytic anemia in the heterozygote; reticulocytosis and Heinz bodies ELECTROPHORESIS Hb X moves with Hb A in conventional electrophoresis at alkaline pH; Hb X moves like Hb A1c on IEF CHROMATOGRAPHY Not reported; the betaX and betaA chains separate in reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAG->AAG at codon 127 FUNCTION STUDIES Probably normal STABILITY Unstable OCCURRENCE Found in a 9-year-old French boy; parents are normal OTHER INFORMATION Quantity in the heterozygote ~30% REFERENCES 1. Baudin-Chich, V., Wajcman, H., Gombaud-Saintonge, G., Arous, N., Riou, J., Briere, J., and Galacteros, F.: Hemoglobin, 12:179, 1988. Hb Dieppe beta127(H5)Gln->Arg CONTACT alpha1beta1 contact HEMATOLOGY Chronic anemia in the heterozygote; thalassemic; reticulocytosis; no Heinz bodies ELECTROPHORESIS No abnormality detected CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES A CAG->CGG mutation at codon 127 FUNCTION STUDIES Not reported STABILITY Highly unstable OCCURRENCE Found in a 31-year-old French female OTHER INFORMATION Patient required occasional blood transfusions; she has elevated Hb F (~18%) and an alpha/beta in vitro chain synthesis ratio of 2.1 REFERENCES 1. Girodon, E., Ghanem, N., Vidaud, M., Riou, J., Martin, J., Galacteros, F., and Goossens, M.: Ann. Hematol., 65:188, 1992. Hb J-Guantanamo beta128(H6)Ala->Asp CONTACT External; alpha1beta1 contact HEMATOLOGY Mild hemolytic anemia with target cells in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves ahead of Hb A CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion of betaX chain; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCT->GAT at codon 128 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in three members of a Cuban family, a Chilean newborn, a Chinese family, a family from Benin, and in a Japanese family OTHER INFORMATION Quantity in the heterozygote 36-38%; found in combination with Hb C REFERENCES 1. Martinez, G., Lima, F., and Colombo, B.: Biochim. Biophys. Acta, 491:1, 1977. 2. Wajcman, H., Baudin-Chich, V., Kister, J., Feo, C., Gombaud-Saintonge, G., Bohn, B., Marden, M., Pagnier, J., Poyart, C., Dode, C., Galacteros, F., Blouquit, Y., Cynober, T., and Tchernia, G.: Am. J. Hematol., 28:170, 1988. 3. Zhu, L.H., Li, M., and Wang, S.J.: Hemoglobin, 12:189, 1988. 4. Sciarratta, G.V., Ivaldi, G., and Moruzzi, F.: Hemoglobin, 14:115, 1990. 5. Yamagishi, Y., Ikeda, K., Takahara, J., Irino, S., Hasui, H., Fujiwara, T., Kaji, Y., Harano, T., and Harano, K.: Hemoglobin, 17:379, 1993. Hb J-Taichung beta129(H7)Ala->Asp CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves ahead of Hb A CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 129 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a 14-year-old Chinese female OTHER INFORMATION Quantity in the heterozygote 41% REFERENCES 1. Blackwell, R.Q., Yang, H-J., and Wang, C-C.: Biochim. Biophys. Acta, 194:1, 1969. Hb K-Cameroon beta129(H7)Ala->Asp or Glu (characterization was incomplete) CONTACT Internal HEMATOLOGY Apparently normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves ahead of Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 129 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a female blood donor from Cameroon OTHER INFORMATION Quantity in the heterozygote 75%; found in combination with Hb S; characterization by protein analysis was incomplete; codon 129 is GCC (Ala), that can be mutated to GAC (Ala-> Asp) but not easily to GAA or GAG (Ala->Glu) REFERENCES 1. Allan, N., Beale, D., Irvine, D., and Lehmann, H.: Nature, 208:658, 1965. Hb Crete beta129(H7)Ala->Pro CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A do not separate with standard techniques; Hb X moves ahead of Hb A by IEF CHROMATOGRAPHY Hb X was isolated on a Bio-Rex 70 column STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fin-gerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->CCC at codon 129 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Unstable OCCURRENCE Found in three members of a Greek family living in New York OTHER INFORMATION Found in combination with betao- and (deltabeta)o-thal REFERENCES 1. Maniatis, A., Bousios, Th., Nagel, R.L., Balazs, T., Ueda, Y., Bookchin, R.M., and Maniatis, G.M.: Blood, 54:54, 1979. Hb La Desirade beta129(H7)Ala->Val CONTACT Internal HEMATOLOGY Probably normal in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures; Hb X was slightly more anodal than Hb A on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GTC at codon 129 FUNCTION STUDIES Decreased oxygen affinity STABILITY Unstable OCCURRENCE Found in two unrelated Black families OTHER INFORMATION Occurred in combination with betao-thal and with Hb C REFERENCES 1. Merault, G., Keclard, L., Garin, J., Poyart, C., Blouquit, Y., Arous, N., Galacteros, F., Feingold, J., and Rosa, J.; Hemoglobin, 10:593, 1986. Hb Wien beta130(H8)Tyr->Asp CONTACT Internal HEMATOLOGY Heinz body hemolytic anemia in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A by conventional techniques CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TAT->GAT at codon 130 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in an Australian male and his daughter, and in a German male OTHER INFORMATION Quantity in the heterozygote ~25% REFERENCES 1. Kleihauer, E. and Betke, K.: Klin. Wschr., 50:907, 1972. 2. Lorkin, P.A., Pietschmann, H., Braunsteiner, H., and Lehmann, H.: Acta Haematol., 51:351, 1974. Hb Nevers beta130(H8)Tyr->Ser CONTACT Internal HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.49-0.54 l/l) ELECTROPHORESIS No separation by standard procedures; Hb X focuses like Hb A1c by IEF CHROMATOGRAPHY No separation reported, but betaX and betaA chains do separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of an AE-betaX+betaA mixture; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation TAT->TCT at codon 130 FUNCTION STUDIES Slight increase in oxygen affinity STABILITY Mildly unstable OCCURRENCE Found in members of a French Caucasian family OTHER INFORMATION Quantity in the heterozygote 33-36% REFERENCES 1. Keclard, L., Campier, A., Merault, G., Auperin, A., Riou, J., Rosa, J., and Galacteros, F.: Hemoglobin, 14:103, 1990. Hb Camden beta131(H9)Gln->Glu ALSO KNOWN AS Tokuchi; Motown CONTACT Internal; alpha1beta1 contact HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; at acidic pH Hb X moves close to Hb F CHROMATOGRAPHY Hb X and Hb A separate by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAG->GAG at codon 131 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in several Black families and in a Japanese family OTHER INFORMATION Quantity in the heterozygote 35-46%; found in combination with Hb S and with alpha-thal REFERENCES 1. Wade-Cohen, P.T., Yates, A., Bellingham, A.J., and Huehns, E.R.: Nature, 243: 467, 1973. 2. Hubbard, M., Wilson, J.B., Wrightstone, R.N., Efremov, G.D., and Huisman, T.H.J.: Acta Haematol., 54:53, 1975. 3. Ohba, Y., Miyaji, T., Matsuoka, M., Ueda, S., Iuchi, I., and Shibata, S.: Acta Haematol. Jap., 38:1, 1975. Hb Shelby beta131(H9)Gln->Lys NOTE: This variant was previously identified as having the glutamine residue at beta131 deleted and was named Hb Leslie or Hb Deaconess; correction was made in Refs. 4 and 5 CONTACT Internal; alpha1beta1 contact HEMATOLOGY Nearly normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X migrates in the Hb F position on cellulose acetate; at acidic pH Hb X moves between Hb S and Hb C CHROMATOGRAPHY Hb X and Hb A readily separate in cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting and cation exchange HPLC; amino acid analysis; sequencing DNA ANALYSES A CAG->AAG mutation at codon 131 (Ref. 6) FUNCTION STUDIES Normal STABILITY Mildly unstable OCCURRENCE Found mainly in a few Black families OTHER INFORMATION Quantity in the heterozygote ~35%; has been found in combination with Hb S, Hb C, alpha-, and beta-thal REFERENCES 1. Lutcher, C.L., Wilson, J.B., Gravely, M.E., Stevens, P.D., Chen, C.J., Lindeman, J.G., Wong, S.C., Miller, A., Gottleib, M., and Huisman, T.H.J.: Blood, 47:99, 1976. 2. Felice, A., Abraham, E.C., Miller, A., Stallings, M., and Huisman, T.H.J.: Am. J. Hematol., 5:1, 1978. 3. Carcassi, U.E.F., Pintus, A., Gravely, M.E., and Huisman, T.H.J.: Hemoglobin, 4:195, 1980. 4. Moo-Penn, W.F., Johnson, M.H., McGuffey, J.E., and Jue, D.L.: Hemoglobin, 8:583, 1984. 5. Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 8:595, 1984. 6. Curuk, M.A., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 16:417, 1992. 7. Adachi, K., Surrey, S., Tamary, H., Kim, J., Eck, H.S., Rappaport, E., and Ohene-Frempong, K.: Hemoglobin, 17:329, 1993. Hb Shanghai beta131(H9)Gln->Pro CONTACT Internal; alpha1beta1 contact HEMATOLOGY Hemolytic anemia in the heterozygote; reticulocytosis ELECTROPHORESIS No separation of Hb X and Hb A by routine analyses CHROMATOGRAPHY No separation reported; the betaX and betaA chains separate by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAG->CCG at codon 131 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in members of a Chinese family OTHER INFORMATION Quantity in the heterozygote ~35% REFERENCES 1. Zeng, Y.T., Ren, Z.R., Chen, M.J., Zhao, J.Q., Qiu, X.K., and Huang, S.Z.: Br. J. Haematol., 67:221, 1987. Hb Sarrebourg beta131(H9)Gln->Arg CONTACT Internal; alpha1beta1 contact HEMATOLOGY Iron-deficiency anemia in the carrier ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb F, and between Hb F and Hb S on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported in detail; only final data are presented DNA ANALYSES Not reported; presumed mutation CAG->CGG at codon 131 FUNCTION STUDIES Normal STABILITY Unstable OCCURRENCE Found in a 9-year-old Turkish boy OTHER INFORMATION Hb X comprised ~30% of the total Hb REFERENCES 1. Duwig, I., North, M.L., Barth, J.G., Rieffel, M., Nierengarten, P., Arous, N., Riou, J., and Galacteros, F.: Abstract, Nouv. Rev. Fr. d'Hematol., 29:344, 1987. Hb K-Woolwich beta132(H10)Lys->Gln CONTACT External; near central cavity HEMATOLOGY Normal in heterozygotes and homozygotes ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves like Hb J; Hb X moves like Hb F at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of the peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAA->CAA at codon 132 FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in several Black families from the West Indies, Ghana, and the Ivory Coast OTHER INFORMATION Quantity in the heterozygote 28-40%; in the homozygous state 95.6%; found in combination with Hb S, Hb C, alpha-, and beta+-thal REFERENCES 1. Allan, N., Beale, D., Irvine, D., and Lehmann, H.: Nature, 208:658, 1965. 2. Ringelhann, B., Konotey-Ahulu, F.I.D., Talapatra, N.C., Nkrumah, F.K., Wiltshire, B.G., and Lehmann, H.: Acta Haematol., 45:250, 1971. 3. Cabannes, R., Renaud, R., Mauran, H., Pennors, H., Charlesworth, D., Price, B.G., and Lehmann, H.: Nouv. Rev. Fr. d'Hematol., 12:289, 1972. 4. Cabannes, R., Amegnizin, P., Sangare, P., Arne, D., Casey, R., and Lehmann, H.: J. Med. Genet., 17:183, 1980. Hb Yamagata beta132(H10)Lys->Asn CONTACT External; near central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A were separated by IEF; Hb X moves faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Two mutations have been observed: AAA->AAC and AAA-> AAT at codon 132 FUNCTION STUDIES Slightly decreased oxygen affinity STABILITY Normal OCCURRENCE Found in members of a Japanese family OTHER INFORMATION Quantity in the heterozygote 40-45% REFERENCES 1. Harano, T., Harano, K., Ueda, S., Imai, K., and Marubashi, S.: Hemoglobin, 14: 207, 1990. 2. Han, J.Y., Wee, J.H., Kim, J.M., Kim, J.Y., Kim, I.H., and Rodgers, G.P.: Hemoglobin, in press (1996). Hb Cook beta132(H10)Lys->Thr CONTACT External; near central cavity HEMATOLOGY About normal in the heterozygote ELECTROPHORESIS Hb X is slightly faster than Hb A at alkaline pH; Hb X moves like Hb F at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES An AAA->ACA mutation at codon 132 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 28-year-old Thai female OTHER INFORMATION Quantity in the heterozygote ~55% REFERENCES 1. Hutt, P.J., Griffin, T., Fairbanks, V., Hoyer, J., and Thibodeau, S.: Blood, 86: 649a (Suppl. 1), 1995. Hb Extremadura beta133(H11)Val->Leu CONTACT Internal HEMATOLOGY Mild hemolytic anemia with splenomegaly; Heinz bodies; reticulocytosis ELECTROPHORESIS No separation reported CHROMATOGRAPHY No separation reported; the betaX and betaA chains separate by reversed phase HPLC; (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->CTG at codon 133 FUNCTION STUDIES Not reported STABILITY Slightly unstable OCCURRENCE Found as a de novo mutation in a 27-year-old Spanish female OTHER INFORMATION Quantity in the heterozygote ~38% (reversed phase HPLC) REFERENCES 1. Villegas, A., Martin, G., Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 13:505, 1989. Hb North Shore beta134(H12)Val->Glu ALSO KNOWN AS North Shore-Caracas CONTACT Internal; central cavity HEMATOLOGY Mild microcytic anemia in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GAG at codon 134 FUNCTION STUDIES Normal STABILITY Unstable OCCURRENCE Found in members of a family with an English mother (carrier) and a Venezuelan father, and in members of a family of Anglo-Celtic ancestry living in Australia OTHER INFORMATION Quantity in the heterozygote 35%; found in combination with Hb S causing a mild sickle cell disease REFERENCES 1. Brennan, S.O., Jones, K.O.A., Crethar, L., Arnold, B.J., Fleming, P.J., and Winterbourn, C.C.: Biochim. Biophys. Acta, 494:403, 1977. 2. Arends, T., Lehmann, H., Plowman, D., and Stathopoulou, R.: FEBS Lett., 80: 261, 1977. 3. Smith, C.M., II, Hedlund, B., Cich, J.A., Tukey, D.P., Olson, M., Steinberg, M.H., and Adams, J.G., III: Blood, 61:378, 1983. 4. Gurney, H., Baig, I., Gordon, S., Phadke, K., Kearsley, H., Fleming, P., Wyatt, K., and Hughes, W.: Pathology, 19:62, 1987. Hb Altdorf beta135(H13)Ala->Pro CONTACT Central cavity HEMATOLOGY Moderate hemolytic anemia in the heterozygote ELECTROPHORESIS No separation with standard techniques CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of impure AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GCT->CCT at codon 135 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity STABILITY Unstable OCCURRENCE Found in members of an Italian family OTHER INFORMATION Quantity in the heterozygote 35% REFERENCES 1. Marti, H.R., Winterhalter, K.H., Di Iorio, E.E., Lorkin, P.A., and Lehmann, H.: FEBS Lett., 63:193, 1976. Hb Beckman beta135(H13)Ala->Glu (or perhaps Asp) NOTE: An Ala->Glu change would require a GCA or GCG mutation to GAA or GAG. The codons GCA and GCG do not occur in the beta-globin gene; GCA is in the gamma gene and GCG in the alpha gene CONTACT Central cavity HEMATOLOGY Chronic anemia; microcytosis; reticulocytosis ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A CHROMATOGRAPHY Not reported; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; analysis of tryptic peptides by reversed phase HPLC; amino acid analysis; FAB mass spectrometry DNA ANALYSES Not reported; presumed mutation GCT->GAT at codon 135 that corresponds to an Ala->Asp replacement FUNCTION STUDIES Decreased oxygen affinity STABILITY Unstable OCCURRENCE Found in a Black female OTHER INFORMATION None REFERENCES 1. Rahbar, S., Lee, T., and Asmeron, Y.: Blood, 78:204a (Suppl. 1), 1991. Hb Hope beta136(H14)Gly->Asp CONTACT Central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves slightly faster than Hb A; best separation by IEF CHROMATOGRAPHY Hb X and Hb A separate in cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by chromatography or by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGT->GAT at codon 136 FUNCTION STUDIES Decreased oxygen affinity and cooperativity; normal Bohr effect STABILITY Mildly unstable OCCURRENCE Found in several Black families, in Japanese, Thai, Laotian, and Cuban families OTHER INFORMATION Quantity in the heterozygote 40-50%; found in combination with Hb S, Hb E, alpha-thal-2 (-3.7 kb), and with beta-thal REFERENCES 1. Minnich, V., Hill, R.J., Khuri, P.D., and Anderson, M.E.: Blood, 25:830, 1965. 2. Moo-Penn, W., Jue, D., George, B., Ramsey, N., and Schmidt, R.M.: Am. J. Clin. Pathol., 63:87, 1975. 3. Hubbard, M., Wilson, J.B., Wrightstone, R.N., Efremov, G.D., and Huisman, T.H.J.: Acta Haematol., 54:53, 1975. 4. Steinberg, M.H., Lovell, W.J., Wells, S., Coleman, M., Dreiling, B.J., and Adams, J.G.: J. Lab. Clin. Med., 88:125, 1976. 5. Charache, S., Achuff, S., Winslow, R., and Kazazian, H.: J. Lab. Clin. Med., 93:316, 1979. 6. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., and Nakai, T.: Hemoglobin, 7:263, 1983. 7. Martinez, G. and Colombo, B.: Hemoglobin, 8:519, 1984. 8. Pillers, D.M., Jones, M., Head, C., and Jones, R.T.: Hemoglobin, 16:81, 1992. 9. Rahbar, S., Nozari, G., Asmerom, Y., Martin, P.A., Yeh, C.H., and Lee, T.D.: Hemoglobin, 16:421, 1992. Hb Brockton beta138(H16)Ala->Pro CONTACT Internal; central cavity HEMATOLOGY Moderate hemolytic anemia with reticulocytosis ELECTROPHORESIS No separation observed CHROMATOGRAPHY No separation observed; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCT->CCT at codon 138 FUNCTION STUDIES Appears normal STABILITY Unstable OCCURRENCE Found in a Caucasian female and in a 12-year-old Turkish girl; parents are not affected OTHER INFORMATION About 20-25% of the Hb in hemolysate is heat labile REFERENCES 1. Moo-Penn, W.F., Jue, D.L., Johnson, M.H., Bechtel, K.C., and Patchen, L.C.: Hemoglobin, 4:347, 1980. 2. Ulukutlu, L., Ozsahin, H., Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 13:509, 1989. Hb Geelong beta139(H17)Asn->Asp CONTACT Central cavity HEMATOLOGY Anemia in the carrier who was also heterozygous for a beta+-thal allele; reticulocytosis ELECTROPHORESIS No separation of Hb X and Hb A was reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis; Dansyl-Edman degradation confirmed the Asn->Asp mutation at beta139 DNA ANALYSES Not reported; presumed mutation AAT->GAT at codon 139 FUNCTION STUDIES Normal STABILITY Mildly unstable OCCURRENCE Found in a 43-year-old German woman of Polish-Russian descent; family studies were not possible OTHER INFORMATION Quantity of Hb X in the proband estimated at 15-20%; Hb A2 6.7%; Hb F 1.5%; the beta+-thal was not identified REFERENCES 1. Como, P.F., Hocking, D.R., Swinton, G.W., Trent, R.J., Holland, R.A.B., Tibben, E.A., Wilkinson, T., and Kronenberg, H.: Hemoglobin, 15:85, 1991. Hb Hinsdale beta139(H17)Asn->Lys CONTACT Central cavity HEMATOLOGY Nearly normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X migrates in the position of Hb F; at acidic pH Hb X has a mobility like Hb S CHROMATOGRAPHY No specific information provided STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAT->AAC or AAA at codon 139 FUNCTION STUDIES Decreased oxygen affinity and reduced cooperativity STABILITY Normal OCCURRENCE Found in three members of one family OTHER INFORMATION Quantity in the heterozygote estimated at 45-46% REFERENCES 1. Moo-Penn, W.F., Johnson, M.H., Jue, D.L., and Lonser, R.: Hemoglobin, 13:455, 1989. Hb Aurora beta139(H17)Asn->Tyr CONTACT Central cavity HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.49 l/l) ELECTROPHORESIS No separation by standard techniques at alkaline pH; Hb X occupies the position of Hb F on acid agar electrophoresis and on IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES An AAT->TAT mutation at codon 139 FUNCTION STUDIES Increased oxygen affinity of whole blood STABILITY Normal OCCURRENCE Found in a 73-year-old Dutch female living in Canada OTHER INFORMATION Quantity of the variant estimated at ~50%; alpha-thal is absent REFERENCES 1. Lafferty, J., Ali, M., Matthew, K., Eng, B., Patterson, M., and Waye, J.S.: Hemoglobin, 19:335, 1995. Hb Saint-Jacques beta140(H18)Ala->Thr CONTACT Internal HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.56 l/l) ELECTROPHORESIS No separation obtained CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX and betaA chains; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->ACC at codon 140 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect STABILITY Normal OCCURRENCE Found in a 36-year-old Caucasian male living in France OTHER INFORMATION None REFERENCES 1. Rochette, J., Varet, B., Boissel, J.P., Clough, K., Labie, D., Wajcman, H., Bohn, B., Magne, P., and Poyart, C.: Biochim. Biophys. Acta, 785:14:1984. Hb Himeji beta140(H18)Ala->Asp CONTACT Internal HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A can be separated by routine methodology; Hb X moves faster than Hb A; excellent separation by IEF CHROMATOGRAPHY Hb X and Hb A separate in cation exchange HPLC; the betaX and betaA chains separate by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 140 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect STABILITY Slightly unstable OCCURRENCE Found in a 52-year-old Japanese male, and in two members of a Portuguese family OTHER INFORMATION Quantity in the heterozygote ~21%; increased binding of glucose at the amino terminus of the beta chain REFERENCES 1. Ohba, Y., Miyaji, T., Murakami, M., Kadowaki, S., Fujita, T., Oimomi, M., Hata-naka, H., Ishikawa, K., Baba, S., Hitaka, K., and Imai, K.: Hemoglobin, 10:109, 1986. 2. Martins, M.C., Rosado, L., Wilson, J.B., Kutlar, A., Hu, H., and Huisman, T.H.J.; Hemoglobin, 13:411, 1989. 3. Lavinha, J., Faustino, P., Osorio-Almeida, L., Hattori, Y., Ohba, Y., and Martins, M.C.: Hemoglobin, 15:137, 1991. Hb Puttelange beta140(H18)Ala->Val CONTACT Internal HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.56 l/l) ELECTROPHORESIS No separation with routine methodology; Hb X moves slightly behind Hb A in IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES The betaX and betaA chains were separated by reversed phase HPLC and digested with trypsin; the peptides were separated by reversed phase HPLC; amino acid analysis; mass spectrometry DNA ANALYSES Not reported; presumed mutation GCC->GTC at codon 140 FUNCTION STUDIES Increased oxygen affinity; low cooperativity STABILITY Unstable OCCURRENCE Found in three members of a French family OTHER INFORMATION None REFERENCES 1. Wajcman, H., Prome, D., North, M.L., Duwig, I., Kister, J., Bergerat, J.P., Ober-ling, F., Groell, J.J., Lampert, E., Lonsdorfer, J., and Galacteros, F.: Abstract, Journees Scientifiques du Club de L'Hemoglobine, Strasbourg, France, June 1993. Hb Olmsted beta141(H19)Leu->Arg CONTACT Internal; heme contact HEMATOLOGY Heinz body hemolytic anemia in the heterozygote ELECTROPHORESIS No separation reported except of the betaX and betaA chains on starch gel or cellulose acetate in the presence of 6 M urea CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CTG->CGG at codon 141 FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in a 12-year-old Caucasian male but not his parents OTHER INFORMATION Quantity in the heterozygote reported as 5-10% REFERENCES 1. Fairbanks, V.F., Opfell, R.W., and Burgert, E.O.: Am. J. Med., 46:344, 1969. 2. Lorkin, P.A., Lehmann, H., and Fairbanks, V.F.: Biochim. Biophys. Acta, 386: 256, 1975. Hb Ohio beta142(H20)Ala->Asp CONTACT External; central cavity; 2,3-DPG pocket HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.54-0.58 l/l) ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; Hb X moves faster than Hb A; Hb X moves between Hb A and Hb F at acidic pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->GAC at codon 142 FUNCTION STUDIES Increased oxygen affinity; reduced Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in three members of a Caucasian family of Scottish-English ancestry OTHER INFORMATION Quantity in the heterozygote 47.7% REFERENCES 1. Moo-Penn, W.F., Schneider, R.G., Shih, T-B., Jones, R.T., Govindarajan, S., Govindarajan, P.G., and Patchen, L.C.: Blood, 56:246, 1980. Hb Toyoake beta142(H20)Ala->Pro CONTACT External; central cavity; 2,3-DPG pocket HEMATOLOGY Normal Hb level but persistent hemolysis in the heterozygote ELECTROPHORESIS A diffuse band is observed between Hb A and Hb A2 at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAEcellulose chromatography; Hb X elutes between Hb A and Hb A2 STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GCC->CCC at codon 142 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Unstable OCCURRENCE Found in a 21-year-old Japanese male but not in the parents OTHER INFORMATION Quantity in the heterozygote perhaps 28%; the variant readily loses heme REFERENCES 1. Ohba, Y., Miyaji, T., Hattori, Y., Fuyuno, K., and Matsuoka, M.: Hemoglobin, 4:307, 1980. 2. Hirano, M., Ohba, Y., Imai, K., Ino, T., Morishita, Y., Matsui, T., Shimizu, S., Sumi, H., Yamamoto, Ki., and Miyaji, T.: Blood, 57:697, 1981. Hb Abruzzo beta143(H21)His->Arg CONTACT External; central cavity; 2,3-DPG binding site HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.45-0.69 l/l) ELECTROPHORESIS Hb X and Hb A can be separated at alkaline pH; it moves between Hb F and Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CGC at codon 143 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect; normal cooperativity in the presence of phosphates; cooperativity is reduced in the absence of phosphates STABILITY Normal (?) OCCURRENCE Found in a few Italian families OTHER INFORMATION Found in combination with beta-thal REFERENCES 1. Tentori, L., Carta Sorcini, M., and Brecella, C.; Clin. Chim. Acta, 38:258, 1972. 2. Chiarioni, T., Nardi, E., Papa, G., Sasso, G.F., and Tentori, L.: Nouv. Rev. Fr. d'Haematol., 14:67, 1974. 3. Chiancone, E., Norne, J.E., Bonaventura, J., Bonaventura, C., and Forsen, S.: Biochim. Biophys. Acta, 336:403, 1975. 4. Bonaventura, C., Bonaventura, J., Amiconi, G., Tentori, L., Brunori, M., and Antonini, E.: J. Biol. Chem., 250:6273, 1975. 5. Bonaventura, J., Bonaventura, C., Amiconi, G., Tentori, L., Brunori, M., and Antonini, E.: J. Biol. Chem., 250:6278, 1975. Hb Little Rock beta143(H21)His->Gln CONTACT External; central cavity; 2,3-DPG binding site HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation with standard methodology CHROMATOGRAPHY Hb X was isolated by CM-cellulose chromatography; Hb X elutes before Hb A STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CAA or CAG at codon 143 FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in a 55-year-old male OTHER INFORMATION Quantity in the heterozygote about 50% REFERENCES 1. Bromberg, P.A., Alben, J.O., Bare, G.H., Balcerzak, S.P., Jones, R.T., Brimhall, B., and Padilla, F.: Nature, 243:177, 1973. 2. Perutz, M.F.: Nature, 243:180, 1973. 3. Bare, G.H., Alben, J.O., Bromberg, P.A., Jones, R.T., Brimhall, B., and Padilla, F.: J. Biol. Chem., 249:773, 1974. Hb Syracuse beta143(H21)His->Pro CONTACT External; central cavity; 2,3-DPG binding site HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation with standard procedures; good separation by IEF; Hb X moves slightly faster than Hb A CHROMATOGRAPHY Hb X was isolated by CM-cellulose chromatography; Hb X elutes slightly ahead of Hb A STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CCC at codon 143 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect; no cooperativity STABILITY Not reported OCCURRENCE Found in six members in four generations of a Caucasian family, and in a 22-year-old Japanese female OTHER INFORMATION Quantity in the heterozygote 40% REFERENCES 1. Jensen, M., Oski, F.A., Nathan, D.G., and Bunn, H.F.: J. Clin. Invest., 55:469, 1975. 2. Iuchi, I., Hidaka, K., Shimasaki, S., and Mizuta, W.: Kawasaki Med. J., 10:21, 1984. Hb Rancho Mirage beta143(H21)His->Asp CONTACT External; central cavity; 2,3-DPG binding site HEMATOLOGY Mild anemia in the heterozygote (PCV 0.30 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; Hb X moves like Hb F at acidic pH CHROMATOGRAPHY No data presented; the betaX and betaA chains can be separated by CM-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->GAC at codon 143 FUNCTION STUDIES Increased oxygen affinity; normal in the presence of 2,3-DPG; decreased cooperativity; decreased alkaline Bohr effect STABILITY Normal OCCURRENCE Found in a 17-year-old male OTHER INFORMATION Quantity in the heterozygote ~53% REFERENCES 1. Moo-Penn, W.F., Hine, T.K., Johnson, M.H., Jue, D.L., Holland, S., George, S., Pierce, A.M., Michalski, L.A., and McDonald, M.J.: Hemoglobin, 16:35, 1992. Hb Old Dominion beta143(H21)His->Tyr CONTACT External; central cavity; 2,3-DPG binding site HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Not reported CHROMATOGRAPHY Hb X moves faster than Hb A in cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->TAC at codon 143 FUNCTION STUDIES Increased oxygen affinity STABILITY Not reported OCCURRENCE Found in a young diabetic male OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Fairbanks, V., McCormick, D., Horn, A., Jones, R., Shih, D., Hoyer, J., Madden, B.J., and Kubik, K.: Blood, 86:647a (Suppl. 1), 1995. Hb Andrew-Minneapolis beta144(HC1)Lys->Asn CONTACT External HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.52-0.57 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; Hb X moves between Hb A and Hb F at acidic pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing; mass spectrometry DNA ANALYSES Not reported; presumed mutation AAG->AAT or AAC at codon 144 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect; normal cooperativity and 2,3-DPG effect STABILITY Not reported OCCURRENCE Found in eight members of a family of unknown ethnic origin, and in a Bulgarian family OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Zak, S.J., Brimhall, B., Jones, R.T., and Kaplan, M.E.: Blood, 44:543, 1974. 2. Hebbel, R.P., Kronenberg, R.S., and Eaton, J.W.: J. Clin. Invest., 60:1211, 1977. 3. Tasheva, E.S., Zareva, Z.Z., Tupozova, S.T., and Molchanova, T.P.: Hemoglobin, 14:227, 1990. Hb Mito beta144(HC1)Lys->Glu CONTACT External HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.46 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves faster than Hb A; Hb X migrates anodally to Hb A on IEF CHROMATOGRAPHY Not reported; the betaX chain was readily isolated by CM-52 chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->CAG at codon 144 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect; normal cooperativity STABILITY Normal OCCURRENCE Found in a 63-year-old Japanese female OTHER INFORMATION Quantity in the heterozygote 42-43% REFERENCES 1. Harano, K., Harano, T., Ueda, S., Ohkushi, T., and Imai, K.: FEBS Lett., 192: 7578, 1985. Hb Bethesda beta145(HC2)Tyr->His CONTACT Internal; alpha2beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.60-0.69 l/l) ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; at acidic pH, Hb X moves between Hb A and Hb S, closer to Hb A CHROMATOGRAPHY Hb X was isolated on a column of CM-cellulose in the cold STRUCTURE STUDIES Tryptic digestion of betaX chain or total Hb; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase A DNA ANALYSES Not reported; presumed mutation TAT->CAT at codon 145 FUNCTION STUDIES Increased oxygen affinity; no cooperativity; normal Bohr effect and 2,3-DPG level STABILITY Normal OCCURRENCE Found in a 12-year-old Chinese family but not in the parents, and in six members of a Canadian family OTHER INFORMATION Quantity in the heterozygote 45% REFERENCES 1. Bunn, H.F., Bradley, T.B., Davis, W.E., Drysdale, J.W., Burke, J.F., Beck, W.S., and Lauer, M.B.: J. Clin. Invest., 51:2299, 1972. 2. Adamson, J.W., Hayashi, A., Stamatoyannopoulos, G., and Burger, W.F.: J. Clin. Invest., 51:2883, 1972. 3. Olson, J.S. and Gibson, Q.H.: J. Biol. Chem., 247:3662, 1972. 4. Schmidt, R.M., Jue, D.L., Ali, M.A.M., Lyonnais, J., and Moo-Penn, W.F.: Am. J. Clin. Pathol., 66:449, 1976. Hb Rainier beta145(HC2)Tyr->Cys CONTACT Internal; alpha2beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.45-0.52 l/l) ELECTROPHORESIS No separation observed CHROMATOGRAPHY Excellent separation of Hb X and Hb A on a CM-Sephadex column STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not reported; presumed mutation TAT->TGT at codon 145 FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; normal Bohr effect STABILITY Normal OCCURRENCE Found in several members of two Caucasian families, and in members of a Canadian family of Greek descent OTHER INFORMATION Quantity in the heterozygote 37-44%; increased resistance to alkali denaturation REFERENCES 1. Stamatoyannopoulos, G., Yoshida, A., Adamson, J., and Heinenberg, S.: Science, 159: 741, 1968. 2. Adamson, J.W., Parer, J.T., and Stamatoyannopoulos, G.: J. Clin. Invest., 48:1376, 1969. 3. Nagai, M., Sugita, Y., and Yoneyama, Y.: J. Biol. Chem., 247:285, 1972. 4. Greer, J. and Perutz, M.F.: Nature, 230:261, 1971. 5. Dingle, B., Farquharson, H., Williams, D., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 3:209, 1979. Hb Osler beta145(HC2)Tyr->Asp or Asn ALSO KNOWN AS Fort Gordon; Nancy NOTE: A study has recently appeared identifying a TAT->AAT mutation as the cause for the abnormal Hb Osler in the original family. This mutation corresponds to a Tyr->Asn replacement; the asparagine residue should readily be deaminated to aspartic acid (Ref. 6). Ref. 7 reports a new case with Hb Osler in a Black family; the mutation reported is TAT->GAT or Tyr->Asp. A further comparison of samples is required to solve this little mystery. CONTACT Internal; alpha2beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.62-0.69 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves ahead of Hb A CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography or fingerprinting; amino acid analysis; carboxypeptidase A DNA ANALYSES Not reported; presumed mutation TAT->GAT at codon 145 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in 11 members of a Black family; a 20-year-old Black male in the army; a French female, and in five members of a family of unspecified racial or ethnic background (Ref. 5) OTHER INFORMATION Quantity in the heterozygote 30% REFERENCES 1. Charache, S., Brimhall, B., and Jones, R.T.: Johns Hopkins Med. J., 136:132, 1975. 2. Kleckner, H.B., Wilson, J.B., Lindeman, J.G., Stevens, P.D., Niazi, G., Hunter, E., Chen, C.J., and Huisman, T.H.J.: Biochim. Biophys. Acta, 400:343, 1975. 3. Gacon, G., Wajcman, H., Labie, D., and Vigneron, C.: FEBS Lett., 56:39, 1975. 4. Arnone, A., Gacon, G., and Wajcman, H.: J. Biol. Chem., 251:5875, 1976. 5. Butler, W.M., Spratling, L., Kark, J.A., and Schoomaker, E.B.: Am. J. Hematol., 13:293, 1982. 6. Hutt, P.J., Donaldson, M., Fairbanks, V., Hoyer, J., Thibodeau, S., Moxness, M., Green, M., and Jones, R.: Blood, 86:486a (Suppl. 1), 1995. 7. Kelly, K.M., Kattamis, A., Fortina, P., and Ohene-Frempong, K.: Blood, 86:651a (Suppl. 1), 1995. Hb McKees Rocks beta145(HC2)Tyr->Term CONTACT Internal; alpha2beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.50-0.64 l/l) ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; Hb X moves with Hb F at acidic pH; excellent separation by IEF CHROMATOGRAPHY Hb X can be isolated on a CM-Sephadex column STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase A DNA ANALYSES Not reported; presumed mutation TAT->TAA at codon 145 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect; no cooperativity; unaffected by 2,3-DPG STABILITY Normal OCCURRENCE Found in several members of two Caucasian families OTHER INFORMATION Quantity in the heterozygote ~46% REFERENCES 1. Winslow, R.M., Swenberg, M-L., Gross, E., Chervenick, P.A., Buchman, R.R., and Anderson, W.F.: J. Clin. Invest., 57:772, 1976. 2. Viggiano, G., Wiechelman, K.J., Chervenick, P.A., and Ho, C.: Biochemistry, 17:795, 1978. 3. Rahbar, S., Rea, C., Blume, K., Seltzer, D., and Feiner, R.: Hemoglobin, 7:97, 1983. Hb Hiroshima beta146(HC3)His->Asp NOTE: This variant was originally identified as having the His->Asp replacement at beta143; a correction was made in 1971 (Ref. 5). CONTACT External; alpha2beta1 contact HEMATOLOGY Mild erythrocytosis in the heterozygote (PCV 0.38-0.55 l/l) ELECTROPHORESIS Hb X and Hb A can be separated at alkaline and acidic pH; Hb X moves faster than Hb A in both systems CHROMATOGRAPHY Hb X was isolated on CM-cellulose and Amberlite IRC-50 columns STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase A and B DNA ANALYSES Not reported; presumed mutation CAC->GAC at codon 146 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Not reported OCCURRENCE Found in eight members of a Japanese family OTHER INFORMATION Quantity in the heterozygote 50% REFERENCES 1. Imai, K.: Arch. Biochem. Biophys., 127:543, 1968. 2. Mihara, K., Hayashi, N., Kikuchi, G., and Shibata, S.: Biochem. Biophys. Res. Commun., 32:763, 1968. 3. Hamilton, H.B., Iuchi, I., Miyaji, T., and Shibata, S.: J. Clin. Invest., 48:525, 1969. 4. Nagel, R.L., Gibson, Q.H., and Hamilton, H.B.: J. Clin. Invest., 50:1772, 1971. 5. Perutz, M.F., del Pulsinelli, P., Ten Eyck, L., Kilmartin, J.V., Shibata, S., Iuchi, I., Miyaji, T., and Hamilton, H.B., Nature, 232:147, 1971. Hb York beta146(HC3)His->Pro CONTACT External; alpha2beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS No separation of Hb X and Hb A at alkaline pH; Hb X moves more rapidly to the cathode than Hb A at acidic pH CHROMATOGRAPHY Hb X was isolated on a CM-cellulose column STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; thermolysin, carboxypeptidase A DNA ANALYSES Not reported; presumed mutation CAC->CCC at codon 146 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect, and cooperativity STABILITY Stable OCCURRENCE Found in a 22-year-old Caucasian female OTHER INFORMATION Quantity in the heterozygote 50% REFERENCES 1. Bare, G.H., Bromberg, P.A., Alben, J.O., Brimhall, B., Jones, R.T., Mintz, S., and Rother, I.: Nature, 259:155, 1976. 2. Kosugi, H., Weinstein, A.S., Kikugawa, K., and Asakura, T.: Hemoglobin, 7:205, 1983. 3. Russu, I.M. and Ho, C.: Biochemistry, 25:1706, 1986. Hb Cochin-Port Royal beta146(HC3)His->Arg CONTACT External; alpha2beta1 contact HEMATOLOGY Normal in the heterozygote (PCV 0.43 l/l) ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves between Hb A and Hb S; excellent separation by IEF CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; carboxypeptidases A and B DNA ANALYSES Not reported; presumed mutation CAC->CGC at codon 146 FUNCTION STUDIES Normal oxygen affinity; reduced Bohr effect STABILITY Normal OCCURRENCE Found in two siblings in a French family OTHER INFORMATION Quantity in the heterozygote 48% REFERENCES 1. Wajcman, H., Kilmartin, J.V., Najman, A., and Labie, D.: Biochim. Biophys. Acta, 400:354, 1975. 2. Russu, I.M. and Ho, C.: Biochemistry, 25:1706, 1986. Hb Cowtown beta146(HC3)His->Leu CONTACT External; alpha1beta1 contact HEMATOLOGY Erythrocytosis in the heterozygote (PCV 0.51-0.54 l/l) ELECTROPHORESIS No separation of Hb X and Hb A by standard procedures CHROMATOGRAPHY Hb X was isolated by Bio-Rex 70 chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; carboxypeptidases A and B DNA ANALYSES Not reported; presumed mutation CAC->CTC at codon 146 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect; normal cooperativity STABILITY Normal OCCURRENCE Found in a Caucasian father and son OTHER INFORMATION Quantity in the heterozygote 40-45% REFERENCES 1. Schneider, R.G., Bremner, J.E., Brimhall, B., Jones, R.T., and Shih, T-B.: Am. J. Clin. Pathol., 72:1028, 1979. 2. Perutz, M.F., Fermi, G., and Shih, T-B.: Proc. Natl. Acad. Sci. USA, 81:4781, 1984. Hb Kodaira beta146(HC3)His->Gln CONTACT External; alpha2beta1 contact HEMATOLOGY Normal? The carrier was anemic because of an unrelated cause ELECTROPHORESIS Hb X was detected by IEF; Hb X moves slightly more anodic than Hb A CHROMATOGRAPHY Not reported; the betaX and betaA chains separated by CM-cellulose chromatography (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES A CAC->CAA mutation at codon 146 FUNCTION STUDIES Increased oxygen affinity STABILITY Normal OCCURRENCE Found in a 75-year-old Japanese male OTHER INFORMATION Quantity in the carrier was 49% REFERENCES 1. Harano, T., Harano, K., Kushida, Y., Imai, K., Nishinakamura, R., and Matsunaga, T.: Hemoglobin, 16:85, 1992. Hb A2-Niigata delta1(NA1)Val->Ala CONTACT Amino terminus; 2,3-DPG binding site ELECTROPHORESIS Not reported IEF Hb X moves anodic to Hb A2 CHROMATOGRAPHY Hb X was discovered by cation exchange HPLC; Hb X elutes between Hb A and Hb A1c STRUCTURE ANALYSIS Tryptic digestion of deltaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSIS Not reported; presumed mutation GTG->GCG at codon 1 NOTES Found in three Japanese individuals REFERENCES 1. Harano, T., Harano, K., Kushida, Y., Ueda, S., and Kawakami, H.: Hemoglobin, 15: 335, 1991. Hb A2-Sphakia delta2(NA2)His->Arg CONTACT 2,3-DPG binding site ELECTROPHORESIS Hb X moves slower than Hb A2 but faster than Hb B2 (see delta16) at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography; Hb X elutes ahead of Hb A2 STRUCTURE ANALYSIS Tryptic digestion of AE-deltaX chain; peptides separated by chromatography; amino acid analysis DNA ANALYSIS Not reported; presumed mutation CAC->CGC at codon 2 NOTES Found in families on Crete and in Canada (Indians) REFERENCES 1. Jones, R.T., Brimhall, B., Huehns, E.R., and Barnicot, N.A.: Science, 151:1406, 1966. 2. Vella, F., Wong, S.C., Wilson, J.B., and Huisman, T.H.J.; Can. J. Biochem., 50:841, 1972. Hb A2-NYU delta12(A9)Asn->Lys CONTACT External ELECTROPHORESIS Hb X moves slower than Hb A2; like Hb B2 (see delta16) IEF Same CHROMATOGRAPHY Hb X can be isolated by DEAE-cellulose or Sephadex chromatography; Hb X elutes ahead of Hb A2 STRUCTURE ANALYSIS Tryptic digestion of deltaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSIS Not reported; presumed mutation AAT->AAA at codon 12 NOTES Found in a few Russian, Greek, Ukrainian, Dutch, and Jewish families; also found in combination with beta-thal trait REFERENCES 1. Aksoy, M. and Erdem, S.: Israel J. Med. Sci., 2:310, 1966. 2. Ranney, H.M., Jacobs, A.S., Ramot, B., and Bradley, T.B.: J. Clin. Invest., 48:2057, 1969. 3. Vella, F., Wong, S.C., Wilson, J.B., and Huisman, T.H.J.: Canad. J. Biochem., 50:841, 1972. 4. De Jong, W.W.W. and Went, L.N.: Hum. Hered., 24:32, 1974. 5. Carter, N.D., Casey, R., and Lehmann, H.: Hum. Hered., 25:13, 1974. Hb A2' (or B2) delta16(A13)Gly->Arg CONTACT External ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH IEF Same CHROMATOGRAPHY Hb X can be separated from Hb A and Hb A2 by cation and anion exchange chromatography STRUCTURE ANALYSIS Tryptic digestion of deltaX chain; separation of peptides by fingerprinting, cation exchange chromatography or reversed phase HPLC; amino acid analysis DNA ANALYSIS A GGC->CGC mutation at codon 16 NOTES Hb A2' is the most common delta chain variant; it is found mainly in Black families; it is observed in heterozygotes, homozygotes, in combination with Hb S, Hb C, beta-thal (in cis and in trans) REFERENCES 1. Horton, B.F., Payne, R.A., Bridges, M.T., and Huisman, T.H.J.: Clin. Chim. Acta, 6:246, 1961. 2. Huisman, T.H.J., Punt, K., and Schaad, J.D.G.: Blood, 17:747, 1961. 3. Pearson, H.A. and Moore, M.M.: Am. J. Hum. Genet., 17:125, 1965. 4. Ball, E.W., Meynell, M.J., Beale, D., Kynoch, P., Lehmann, H., and Stretton, A.O.W.: Nature, 209:1217, 1966. 5. Jones, R.T., Brimhall, B., and Huisman, T.H.J.: J. Biol. Chem., 242:5141, 1967. 6. Codrington, J.F., Li, H-W., Kutlar, F., Gu, L-H., Ramachandran, M., and Huisman, T.H.J.: Blood, 76:1246, 1990. Hb A2-Roosevelt delta20(B2)Val->Glu CONTACT External ELECTROPHORESIS Hb X moves like Hb S at alkaline pH IEF Same CHROMATOGRAPHY Hb X can be isolated by DEAE-cellulose chromatography STRUCTURE ANALYSIS Proteolytic digestion of deltaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSIS Not reported; presumed mutation GTG->GAG at codon 20 NOTES Found in members of an Iraqi family REFERENCES 1. Rieder, R.F., Clegg, J.B., Weiss, H.J., Christy, N.P., and Rabinowitz, R.: Biochim. Biophys. Acta, 439:501, 1976. Hb A2-Flatbush delta22(B4)Ala->Glu CONTACT External ELECTROPHORESIS Hb X moves in the position of Hb S at alkaline pH IEF Same CHROMATOGRAPHY Hb X can be isolated by DEAE cellulose chromatography; Hb X elutes after Hb A2 STRUCTURE ANALYSIS Tryptic digestion of deltaX chain; separation of peptides by cation exchange HPLC; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GCA->GAA at codon 22 NOTES Found in a few Black families REFERENCES 1. Ranney, H.M., Jacobs, A.S., Bradley, T.B., and Cordova, F.A.: Nature, 197:164, 1963. 2. Lee, R.C. and Huisman, T.H.J.: Blood, 24:495, 1964. 3. Jones, R.T., Brimhall, B., and Huisman, T.H.J.: J. Biol. Chem., 242:5141, 1967. Hb A2-Victoria delta24(B6)Gly->Asp CONTACT Internal ELECTROPHORESIS Hb X moves with Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE ANALYSIS Tryptic digestion of Hb X; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GGT->GAT at codon 24 NOTES Found in members of an Iraqi family; in association with beta-thal REFERENCES 1. Brennan, S.O., Williamson, D., Smith, M.B., Cauchi, M.N., MacPhee, A., and Carrell, R.W.: Hemoglobin, 8:163, 1984. Hb A2-Yokoshima delta25(B7)Gly->Asp CONTACT External ELECTROPHORESIS Not reported IEF Hb X focuses between Hb A and Hb A2 CHROMATOGRAPHY Hb X was isolated by anion exchange HPLC STRUCTURE ANALYSIS Tryptic digestion of deltaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GGT->GAT at codon 25 NOTES Found in a Japanese family; one member is a homozygote REFERENCES 1. Ohba, Y., Igarashi, M., Tsukahara, M., Nakashima, M., Sanada, C., Ami, M., Arai, Y., and Miyaji, T.: Hemoglobin, 9:613, 1985. Hb A2-Puglia delta26(B8)Glu->Asp CONTACT External; surface crevice ELECTROPHORESIS Hb X moves slightly slower than Hb A2 at alkaline pH IEF About the same CHROMATOGRAPHY Not reported STRUCTURE ANALYSIS Not reported DNA ANALYSIS A GAG->GAC mutation at codon 26 NOTES Found in an Italian family in association with beta-thal (codon 39; C->T) REFERENCES 1. Loudianos, G., Porcu, S., Cossu, P., Tannoia, N., Vitucci, A., Campanale, D., Cao, A., and Pirastu, M.: Hum. Mut., 2:327, 1993. Hb A2-Yialousa delta27(B9)Ala->Ser CONTACT Internal ELECTROPHORESIS Not reported IEF Not reported CHROMATOGRAPHY Not reported STRUCTURE ANALYSIS Not reported DNA ANALYSIS A GCC->TCC mutation at codon 27 NOTES Found in a Cypriot family; occurs in association with a deltaIVS-II 3' acceptor splice site mutation (A->G) REFERENCES 1. Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S.: Blood, 78:3298, 1991. Hb A2-Melbourne delta43(CD2)Glu->Lys CONTACT External ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE ANALYSIS Tryptic digestion of deltaX chain; separation of peptides by cation exchange HPLC; amino acid analysis DNA ANALYSIS Not reported; presumed mutation GAG->AAG at codon 43 NOTES Found in members of an Italian family living in Australia REFERENCES 1. Sharma, R.S., Harding, D.L., Wong, S.C., Wilson, J.B., Gravely, M.E., and Huisman, T.H.J.: Biochim. Biophys. Acta, 359:233, 1974. Hb A2-Agrinio delta43(CD2)Glu->Gly CONTACT External ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH IEF About the same CHROMATOGRAPHY Hb X can readily be separated from Hb A and Hb A2 by cation exchange HPLC methodology STRUCTURE ANALYSIS Not reported DNA ANALYSIS A GAG->GGG mutation at codon 43 NOTES Found in members of a Greek family REFERENCES 1. Papadakis, M., Drakoulakou, O., Papapanagiotou, E., Pessini, D., and Loutradi-Anagnostou, A.: Hemoglobin, 19:295, 1995. Hb A2-Parkville delta47(CD6)Asp->Val CONTACT External ELECTROPHORESIS Hb X moves like Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE ANALYSIS Digestion of deltaX with trypsin; separation of peptides by reversed phase HPLC; sequencing DNA ANALYSIS Not reported; presumed mutation GAT->GTT at codon 47 NOTES Found in members of an Italian family; probably occurred in combination with beta-thal REFERENCES 1. Leung, H., Gilbert, A.T., Fleming, P.J., Wong, J., Hughes, W.G., Hussein, S., and Nash, A.R.: Hemoglobin, 15:407, 1991. Hb A2-Adria delta51(D2)Pro->Arg CONTACT alpha1beta2 contact ELECTROPHORESIS Hb X moves slower than Hb A2 IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE ANALYSIS Tryptic digestion of Hb X; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSIS Not reported; presumed mutation CCT->CGT at codon 51 NOTES Found in members of an Italian family; occurred in association with beta-thal REFERENCES 1. Alberti, R., Tentori, L., Marinucci, M., and Borghesi, V.: Hemoglobin, 2:171, 1978. Hb A2-Indonesia delta69(E13)Gly->Arg CONTACT External ELECTROPHORESIS Hb X is slower than Hb A2 and slightly faster than Hb A2' (delta16) IEF Not reported CHROMATOGRAPHY Hb X can be isolated by cation and anion exchange HPLC STRUCTURE ANALYSIS Tryptic digestion of deltaX chain or of Hb X; separation of peptides by fingerprinting or chromatography; amino acid analysis DNA ANALYSIS Not reported; presumed mutation GGT->CGT at codon 69 NOTES Found at low frequency in the Indonesian and Malay populations; found in association with Hb E and with beta-thal REFERENCES 1. Lie-Injo, L.E., Poey-Oey, H.G., and Mossberger, R.J.: Am. J. Hum. Genet., 20: 470, 1968. 2. Lie-Injo, L.E., Wita, P., Westendorp-Boerma, F., Efremov, G.D., Wilson, J.B., Reynolds, C.A., and Huisman, T.H.J.: Biochim. Biophys. Acta, 229:335, 1971. 3. Ganesan, J. and Lie-Injo, L.E.: Acta Haematol., 59:341, 1978. Hb A2-Grovetown delta75(E19)Leu->Val CONTACT Internal; partly visible ELECTROPHORESIS No difference observed IEF Same CHROMATOGRAPHY Hb X was detected by cation exchange HPLC; Hb X elutes behind Hb A2 STRUCTURE ANALYSIS Not done DNA ANALYSIS A CTG->GTG mutation at codon 75 NOTES Found in a healthy 13-year-old Black female REFERENCES 1. Molchanova, T.P., Postnikov, Y.V., Gu, L-H., and Huisman, T.H.J.: Hemoglobin, 17:289, 1993. Hb A2-Honai delta90(F6)Glu->Val CONTACT External ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X was isolated by cation exchange HPLC; Hb X elutes behind Hb A2 STRUCTURE ANALYSIS Tryptic digestion of AE-deltaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSIS Not reported; presumed mutation GAG->GTG at codon 90 NOTES Found in members of a Japanese family REFERENCES 1. Fujita, S., Ohta, Y., Saito, S., Kobayashi, Y., Naritomi, Y., Kawaguchi, T., Imamura, T., Wada, Y., and Hayashi, A.: Hemoglobin, 9:597, 1985. Hb A2-Sant' Antioco delta93(F9)Cys->Gly CONTACT Internal; partly visible ELECTROPHORESIS No separation reported IEF Not reported CHROMATOGRAPHY Hb X was detected by HPLC STRUCTURE ANALYSIS Not done DNA ANALYSIS A TGT->GGT mutation at codon 93 NOTES Found in a Sardinian family; Hb X may be unstable REFERENCES 1. Galanello, R., Gasperini, D., Perseu, L., Barella, S., Ideo, A., and Cao, A.: Hemoglobin, 18:437, 1994. Hb A2-Wrens delta98(FG5)Val->Met CONTACT Internal; heme to alpha2beta1 contacts ELECTROPHORESIS No separation observed IEF No separation observed CHROMATOGRAPHY No separation observed STRUCTURE ANALYSIS Not done DNA ANALYSIS A GTG->ATG mutation at codon 98 NOTES Found in a Black family; variant is unstable and occurred in association with HPFH REFERENCES 1. Codrington, J.F., Kutlar, F., Harris, H.F., Wilson, J.B., Stoming, T.A., and Huisman, T.H.J.: Biochim. Biophys. Acta, 1009:87, 1989. Hb A2-Canada delta99(G1)Asp->Asn CONTACT Internal; near cavity; alpha2beta1 contact ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH; Hb X cannot be separated from Hb B2 (delta16) IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography; Hb X elutes ahead of Hb A2 STRUCTURE ANALYSIS Tryptic digestion of AE-deltaX chain; separation of peptides by cation exchange HPLC; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GAT->AAT at codon 99 NOTES Found in an Indian family; occurred in association with beta-thal; Hb X has an increased affinity for oxygen REFERENCES 1. Salkie, M.L., Gordon, P.A., Rigal, W.M., Lam, H., Wilson, J.B., Headlee, M.E., and Huisman, T.H.J.: Hemoglobin, 6:223, 1982. Hb A2-Coburg delta116(G18)Arg->His CONTACT External ELECTROPHORESIS Hb X moves slightly faster than Hb S at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE ANALYSIS Tryptic digestion of AE-deltaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation CGT->CAT at codon 116 NOTES Found in a Sicilian family in association with beta-thal REFERENCES 1. Sharma, R.S., Williams, L., Wilson, J.B., and Huisman, T.H.J.: Biochim. Biophys. Acta, 393:379, 1975. Hb A2-Troodos delta116(G18)Arg->Cys CONTACT External ELECTROPHORESIS Not reported IEF Not reported CHROMATOGRAPHY Not done STRUCTURE ANALYSIS Not done DNA ANALYSIS A CGC->TGC mutation at codon 116 NOTES Found in a Cypriot family; occurred in association with Hb A2-Pelendri [delta141(H19)Leu->Pro] REFERENCES 1. Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S.: Blood, 78:3298, 1991. Hb A2-Liangcheng delta117(G19)Asn->Asp CONTACT External; alpha1beta1 contact ELECTROPHORESIS Hb X moves between Hb A and Hb A2 at alkaline pH IEF About the same CHROMATOGRAPHY Hb X can be separated by cation and anion exchange chromatography STRUCTURE ANALYSIS Not reported DNA ANALYSIS An AAC->GAC mutation at codon 117 NOTES Found in a Chinese family (Han nationality) REFERENCES 1. Qin, W-B., Ju, T-L., Yue, X-L., Yan, X-L., Qin, L-Y., Molchanova, T.P., Pobedim-skaya, D.D., and Huisman, T.H.J.: Hemoglobin, 17:463, 1993. Hb A2-Manzanares delta121(GH4)Glu->Val CONTACT External ELECTROPHORESIS Hb X moves slower than Hb A2, about like Hb A2' (delta16) IEF About the same CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography; Hb X is the first Hb fraction that is eluted STRUCTURE ANALYSIS Tryptic digestion of AE-deltaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GAA->GTA at codon 121 NOTES Found in a Spanish family; variant is rather unstable REFERENCES 1. Romero Garcia, C., Navarro, J.L., Lam, H., Webber, B.B., Headlee, M.G., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 7:435, 1983. Hb A2-Zagreb delta125(H3)Gln->Glu CONTACT ELECTROPHORESIS Hb X moves between Hb A and Hb A2 at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X elutes between Hb A2 and Hb A from a DEAE-cellulose column STRUCTURE ANALYSIS Tryptic digestion of AE-deltaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation CAA->GAA at codon 125 NOTES Found in a Yugoslavian (Croatian) family; occurred in association with a (deltabeta)o-thal REFERENCES 1. Juricic, D., Crepinko, I., Efremov, G.D., Lam, H. Webber, B.B., Headlee, M.G., and Huisman, T.H.J.: Hemoglobin, 7:443, 1983. Hb A2-Babinga delta136(H14)Gly->Asp CONTACT Central cavity ELECTROPHORESIS Hb X moves slightly faster than Hb A2 at alkaline pH IEF Not reported CHROMATOGRAPHY Hb X separates from Hb A2 on an anion exchange column STRUCTURE ANALYSIS Tryptic digestion of AE-delta chain; separation of peptides by fingerprinting or cation exchange HPLC; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GGT->GAT at codon 136 NOTES Found in Babinga Pygmies (frequency 1-2%) and also in a few Black families REFERENCES 1. De Jong, W.W.W. and Bernini, L.F.: Nature, 219:1360, 1968. 2. Huisman, T.H.J., Reynolds, C.A., Dozy, A.M., and Wilson, J.B.: Biochim. Biophys. Acta, 175:223, 1969. 3. McRoyan, D.K., Liu, P.I., Mankad, V.N., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 8:413, 1984. Hb A2-Pelendri delta141(H19)Leu->Pro CONTACT Internal; heme contact ELECTROPHORESIS Not reported IEF Not reported CHROMATOGRAPHY Not done STRUCTURE ANALYSIS Not done DNA ANALYSIS A CTG->CCG mutation at codon 141 NOTES Found in a Cypriot family in association with Hb A2-Troodos [delta116(G18)Arg->Cys] REFERENCES 1. Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S.: Blood, 78:3298, 1991. Hb A2-Fitzroy delta142(H20)Ala->Asp CONTACT External; central cavity; 2,3-DPG pocket ELECTROPHORESIS Hb X moves between Hb S and Hb A2 at alkaline pH IEF About the same CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex chromatography STRUCTURE ANALYSIS Tryptic digestion of Hb X; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSIS Not reported; presumed mutation GCC->GAC at codon 142 NOTES Found in a Greek family REFERENCES 1. Williamson, D., Brennan, S.O., Strosberg, H., Whitty, J., and Carrell, R.W.: Hemoglobin, 8:325, 1984. Hb Wayne alpha139 (-A) in alpha2 or alpha1; modified C-terminal sequence: (139)ASN-Thr-Val-Lys-Leu-Glu-Pro-(146)Arg-COOH HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X appears as two bands (one band cathodic and the other anodic to Hb J-Baltimore) in electrophoresis at alkaline pH CHROMATOGRAPHY Hb X elutes faster than Hb A from a cation exchange HPLC column; can also be isolated on DEAE-Sephadex or DEAE-Sephacel columns STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing; Edman degradation DNA ANALYSES Not reported; variation must be the result of a frameshift FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity and Bohr effect STABILITY Stable OCCURRENCE Found in members of three Caucasian families in the USA OTHER INFORMATION Quantity in the heterozygote 12-16% REFERENCES 1. Seid-Akhavan, M., Winter, W.P., Abramson, R.K., and Rucknagel, D.L.: Proc. Natl. Acad. Sci. USA, 73:82, 1976. 2. Huisman, T.H.J., Headlee, M.G., Wilson, J.B., Lam, H., Johnson, S.E.N., and Webber, B.B.: Hemoglobin, 8:1, 1984. Hb Constant Spring (or CS) alpha142, Term->Gln (TAA->CAA in alpha2); modified C-terminal sequence: (142)GLN-Ala-Gly-Ala-Ser-Val-Ala-Val-Pro-Pro-Ala-Arg-Trp- Ala-Ser-Gln-Arg-Ala-Leu-Leu-Pro-Ser-Leu-His-Arg-Pro- Phe-Leu-Val-Phe-(172)Glu-COOH (31 additional residues) HEMATOLOGY Mild hypochromia and microcytosis in the heterozygote ELECTROPHORESIS Two components moving slower than Hb A2 at alkaline pH CHROMATOGRAPHY Hb X was isolated on Amberlite IRC-50 or DEAE-Sephadex columns; separation by cation exchange HPLC not satisfactory STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES A TAA->CAA mutation at codon alpha142 (alpha2); the Hb CS abnormality is now routinely identified through DNA analyses (sequencing of amplified DNA; dot-blot analysis with specific probes; RFLP analysis) FUNCTION STUDIES Not reported STABILITY Unstable OCCURRENCE Found in modest frequencies in many SE Asian populations (China, Vietnam, Laos, Cambodia, India, Malaysia, Indonesia, etc.) OTHER INFORMATION Quantity in heterozygotes 1-2%; homozygotes have higher quantities; Hb CS in combination with an alpha-thal-1 (mostly the SEA type) results in a rather severe form of Hb H disease REFERENCES 1. Milner, P.F., Clegg, J.B., and Weatherall, D.J.: The Lancet, i:729, 1971. 2. Clegg, J.B., Weatherall, D.J., and Milner, P.F.: Nature, 234:337, 1971. 3. Efremov, G.D., Wrightstone, R.N., Huisman, T.H.J., Schroeder, W.A., Hyman, C., Ortega, J., and Williams, K.: J. Clin. Invest., 50:1628, 1971. 4. Lie-Injo, L.E., Baer, A., Lewis, L.N., and Welch, Q.B.: Am. J. Hum. Genet., 25: 382, 1973. 5. Kan, Y.W., Todd, D., and Dozy, A.M.: Br. J. Haematol., 28:103, 1974. 6. Lie-Injo, L.E., Ganesan, J., Clegg, J.B., and Weatherall, D.J.: Blood, 43:251, 1974. 7. Xu, X-M., Zhang, J-Z., and Li, S-K.: Hemoglobin, 18:61, 1994. 8. Smetanina, N.S., Leonova, J.Y., Levy, N., and Huisman, T.H.J.: Acta Haematol., 94:144, 1995. Hb Icaria alpha142, Term->Lys (TAA->AAA in alpha2); modified C-terminal sequence is the same as Hb CS except that residue 142 is LYS HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH CHROMATOGRAPHY Hb X was isolated on an Amberlite IRC-50 column STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by fin-gerprinting; amino acid analysis; sequencing DNA ANALYSES A TAA->AAA mutation at codon alpha142 (alpha2); the Hb Icaria abnormality can best be identified by sequencing of the alpha2 gene or by dot-blot analysis with specific probes FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a female living on the island of Icaria in the Aegean Sea, and in a Macedonian family in combination with alpha-thal-1 OTHER INFORMATION Quantity in the heterozygote less than 1%; found in combination with an alpha-thal-1 [the -(alpha)20.5 kb deletion] causing Hb H disease REFERENCES 1. Clegg, J.B., Weatherall, D.J., Contopolou-Griva, I., Caroutsos, K., Poungouras, P., and Tsevrenis, H.: Nature, 251:245, 1974. 2. Efremov, G.D., Josifovska, O., Nikolov, N., Codrington, J.F., Oner, C., Gonzalez-Redondo, J.M., and Huisman, T.H.J.: Br. J. Haematol., 75:250, 1990. Hb Koya Dora alpha142, Term->Ser (TAA->TCA in alpha2 or alpha1); modified C-terminal sequence is not definitely established but likely similar to Hb CS except that residue 142 is SER HEMATOLOGY Inconclusive ELECTROPHORESIS Hb X moves slower than Hb A2 at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TAA->TCA at codon alpha142 (alpha2 or alpha1); the Hb Koya Dora abnormality can best be detected by sequencing of the alpha genes and dot-blot analysis with specific probes FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in approximately 10% of the Koya Dora tribe from Andhra Pradesh, India OTHER INFORMATION Quantity in the heterozygote 0.5-2%; up to 10% in the homozygote; found in combination with Hb Rampa [alpha95(G2) Pro->Ser] REFERENCES 1. De Jong, W.W.W., Meera Khan, P., and Bernini, L.F.: Am. J. Hum. Genet., 27:81, 1975. Hb Seal Rock alpha142, Term->Glu (TAA->GAA in alpha2); modified C-terminal sequence is the same as as Hb CS except that residue 142 is GLU HEMATOLOGY Mild anemia with microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X moves as two bands, slower than Hb A2 at alkaline pH CHROMATOGRAPHY Hb X can be isolated by anion exchange chromatography; various alpha chain zones are obtained when Hb X is analyzed by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A TAA->GAA mutation at codon alpha142 (alpha2); the Hb Seal Rock abnormality can best be detected by sequencing of the alpha gene or by dot-blot analysis with specific probes FUNCTION STUDIES Increased oxygen affinity STABILITY Not reported OCCURRENCE Found in a few Black families OTHER INFORMATION When present in association with an alpha-thal-2 allele (3.7 kb deletion) a mild Hb H disease is observed REFERENCES 1. Bradley, T.B., Wohl, R.C., and Smith, E.J.: Clin. Res., 23:131A, 1975. 2. Fairbanks, V., Merritt, D., Rodgers, D., Thibodeau, S., Steinberg, M., Coleman, M., and Jones, R.: Blood, 86:657a (Suppl. 1), 1995. Hb Pakse alpha142, Term->Tyr (TAA->TAT at alpha2); C-terminal sequence was not determined because the Hb could not be isolated; it appears likely that it will be the same as Hb CS except that residue 142 is TYR HEMATOLOGY Probably normal in the heterozygote ELECTROPHORESIS Not observed CHROMATOGRAPHY Not observed STRUCTURE STUDIES Not done DNA ANALYSES A TAA->TAT mutation at codon alpha142 (alpha2); the Hb Pakse abnormality can best be detected by sequencing of the alpha2 gene or by dot-blot analysis with specific probes FUNCTION STUDIES Not done STABILITY Not done OCCURRENCE Found in a Laotian family OTHER INFORMATION Observed in associated with alpha-thal-2 REFERENCES 1. Waye, J.S., Eng, B., Patterson, M., Chui, D.H.K., and Olivieri, N.F.: Blood, 83: 3418, 1994. 2. Smetanina, N.S., Leonova, J.Y., Levy, N., and Huisman, T.H.J.: Acta Haematol., 94:144, 1995. Hb Saverne beta143 (-A); abnormal C-terminal sequence: (143)PRO-Ser-Ile-Thr-Lys-Leu-Ala-Phe-Leu-Leu-Ser- Asn-Phe-(156)Tyr-COOH (most likely sequence) HEMATOLOGY Heinz body hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A in IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed frameshift at codon beta143 (-A) FUNCTION STUDIES High oxygen affinity with low cooperativity STABILITY Unstable OCCURRENCE Found in a French female OTHER INFORMATION Quantity in the heterozygote 35% REFERENCES 1. Delanoe-Garin, J., Blouquit, Y., Arous, N., Kister, J., Poyart, C., North, M.L., Bardakdjian, J., Lacombe, C., Rosa, J., and Galacteros, F.: Hemoglobin, 12:337, 1988. Hb Cranston beta144+beta145 (+AA); abnormal C-terminal sequence: (144)Lys-(145)SER-Ile-Thr-Lys-Leu-Ala-Phe- Leu-Leu-Ser-Asn-Phe-(157)Tyr-COOH HEMATOLOGY Compensated hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves close to Hb S at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed frameshift at codon beta145 (+AG) FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and coop-erativity STABILITY Unstable; dissociation of subunits, hybrids OCCURRENCE Found in members of an Italian-American family OTHER INFORMATION Quantity in the heterozygote 30-40% REFERENCES 1. Bunn, H.F., Schmidt, G.J., Haney, D.N., and Dluhy, R.G.: Proc. Natl. Acad. Sci. USA, 72:3609, 1975. 2. McDonald, M.J., Lund, D.P., Bleichman, M., Bunn, H.F., DeYoung, A., Noble, R.W., Foster, B., and Arnone, A.: J. Mol. Biol., 140:357, 1980. 3. Shaeffer, J.R., Schmidt, G.J., Kingston, R.E., and Bunn, H.F.: J. Mol. Biol., 140: 377, 1980. Hb Tak beta147 (+AC); abnormal C-terminal sequence: (147)THR-Lys-Leu-Ala-Phe-Leu-Leu- Ser-Asn-Phe-(157)Tyr-COOH HEMATOLOGY Nearly normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb G at alkaline pH; at acidic pH Hb X moves as Hb S CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed frameshift at terminating codon beta147 (+AC) FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Heat stable but mildly unstable with the isopropanol test OCCURRENCE Found in a few Thai families OTHER INFORMATION Quantity in the heterozygote 35-40%; found in association with beta-thal REFERENCES 1. Flatz, G., Kinderlerer, J.L., Kilmartin, J.V., and Lehmann, H.: The Lancet, i:732, 1971. 2. Imai, K. and Lehmann, H.: Biochim. Biophys. Acta, 412:288, 1975. 3. Lehmann, H., Casey, R., Lang, A., Stathopoulou, R., Imai, K., Tuchinda, S., Vinai, P., and Flatz, G.: Br. J. Haematol., 31:119 (Suppl.), 1975. Hb Thionville alpha1(NA1)Val->Glu; amino terminus extended with a methionyl residue: (-1)Met-(+1)Glu-(+2)Leu-Ser- HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A in IEF CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of the alpha chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GAG at codon alpha1 (alpha2 or alpha1); this prevents the removal of the initiator methionine FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a 78-year-old diabetic patient OTHER INFORMATION Quantity in the heterozygote 21% REFERENCES 1. Vasseur, C., Guillemin, C., Galacteros, F., and Wajcman, H.: Blood, 76:78a (Suppl. 1), 1990. Hb Doha beta1(NA1)Val->Glu; amino terminus extended with a methionyl residue: (-1)Met-(+1)Glu-(+2)His-Leu- HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A in routine electrophoresis at alkaline pH; Hb X moves like Hb F at acidic pH CHROMATOGRAPHY Hb X and Hb A separate in cation exchange HPLC (Hb X elutes faster) and by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->GAG at codon beta1; this prevents the removal of the initiator methionine FUNCTION STUDIES Not reported STABILITY Stable OCCURRENCE Found in members of a Qatari family OTHER INFORMATION Quantity in the heterozygote ~50% REFERENCES 1. Kamel, K., El-Najjar, A., Webber, B.B., Chen, S.S., Wilson, J.B., Kutlar, A., and Huisman, T.H.J.: Biochim. Biophys. Acta, 831:257, 1985. Hb South Florida beta1(NA1)Val->Met; amino terminus extended with a methionyl residue: (-1)Met-(+1)Met-(+2)His-Leu- HEMATOLOGY Probably normal ELECTROPHORESIS Hb X focuses ahead of Hb A in IEF CHROMATOGRAPHY Hb X elutes with Hb A1c in cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTG->ATG at codon beta1; this prevents the removal of the initiator methionine FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in members of a Caucasian family OTHER INFORMATION Quantity in the heterozygote 12-20%; about 20% of the variant is acetylated REFERENCES 1. Boissel, J-P., Kasper, T.J., Shah, S.C., Malone, J.I., and Bunn, H.F.: Proc. Natl. Acad. Sci. USA, 82:8448, 1985. Hb Marseille beta2(NA2)His->Pro; amino terminus extended with a methionyl residue: (-1)Met-(+1)Val-(+2)Pro-Leu- ALSO KNOWN AS Long Island-Marseille HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS No separation at alkaline pH; Hb X moves cathodal to Hb A in citrate agar electrophoresis at pH 6.0 CHROMATOGRAPHY Hb X elutes faster than Hb A from a cation exchange column; the betaX and betaA chains separate in reversed phase HPLC (elution order: betaA, betaX, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation CAC->CCC at codon beta2; this prevents the removal of the initiator methionine FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a French, an American, and an Australian family (two families are known to be of Maltese origin) OTHER INFORMATION Quantity in the heterozygote ~45% REFERENCES 1. Blouquit, Y., Arous, N., Lena, D., Delanoe-Garin, J., Lacombe, C., Bardakdjian, J., Vovan, L., Orsini, A., Rosa, J., and Galacteros, F.: FEBS Lett., 178:315, 1984. 2. Barwick, R.C., Jones, R.T., Head, C.G., Shih, M.F-C., Prchal, J.T., and Shih, D.T-B.: Proc. Natl. Acad. Sci. USA, 82:4602, 1985. 3. Boi, S., Hendy, J., Goodall, I., Gilbert, A., Fleming, P., and Hughes, W.G.: Hemo-globin, 13:515, 1989. Hb F-Malaysia Ggamma1(NA1)Gly->Cys ELECTROPHORESIS Hb FX moves faster than Hb A IEF No information CHROMATOGRAPHY Hb FX was isolated by DEAE-Sephadex chromatography CHAIN SEPARATION No information STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; Dansylation DNA ANALYSES Not reported; presumed mutation GGT->TGT at codon 1 NOTES Found in a Chinese newborn in Kuala Lumpur; Hb FX 12.8% of total Hb or 18.8% of total Hb F REFERENCES 1. Lie-Injo, L.E., Kamuzora, H., and Lehmann, H.; J. Med. Genet., 11:25, 1974. Hb F-Meinohama Ggamma5(A2)Glu->Gly ELECTROPHORESIS Hb FX moves slower than Hb A IEF No information CHROMATOGRAPHY No information CHAIN SEPARATION No information STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GGG at codon 5 NOTES Found in a newborn from Fukuoka, Japan; Hb FX 10% of total Hb (starch block electrophoresis) REFERENCES 1. Ohta, Y., Saito, S., Fujita, S., Wilson, J.B., Lam, H., and Huisman, T.H.J.: Hemoglobin, 5:565, 1981. Hb F-Auckland Ggamma7(A4)Asp->Asn ELECTROPHORESIS Hb FX moves slower than Hb F (between Hb S and Hb C) at alkaline pH IEF No information CHROMATOGRAPHY Hb FX was isolated by anion exchange HPLC CHAIN SEPARATION GgammaX moves like Ggamma STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC at codon 7 NOTES Observed in newborns in New Zealand and in Alabama, USA; Hb FX ~19% of total Hb and 22.5% of total Hb F (DEAE-cellulose chromatography) REFERENCES 1. Carrell, R.W., Owen, M.C., Anderson, R., and Berry, E.: Biochim. Biophys. Acta, 365:323, 1974. 2. Chen, S.S., Wilson, J.B., Webber, B.B., Kutlar, A., and Huisman, T.H.J.: Hemoglobin, 9:531, 1985. Hb F-Albaicin Ggamma8(A5)Lys->Glu or Gln ELECTROPHORESIS Hb FX moves faster than Hb A at alkaline pH IEF No information CHROMATOGRAPHY No information CHAIN SEPARATION GgammaX = 29.2%; Ggamma = 50.6%; Agamma = 20.2% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequence analysis was not possible DNA ANALYSES Not reported; presumed mutation AAG->CAG (Gln) or GAG (Glu) at codon 8 NOTES Found in a Spanish newborn; quantity in the newborn ~29% of total gamma (reversed phase HPLC) REFERENCES 1. de Pablos, J.M., Wilson, J.B., Kutlar, A., Chen, S.S., and Huisman, T.H.J.: Hemoglobin, 10:655, 1986. Hb F-Heather Ggamma12(A9)Thr->Arg ELECTROPHORESIS No information IEF No information CHROMATOGRAPHY No information CHAIN SEPARATION No information STRUCTURE STUDIES No information DNA ANALYSES No information; presumed mutation ACA->AGA at codon 12 NOTES No information REFERENCES 1. T.B. Bradley, personal communication, 1982. Hb F-Catalonia Ggamma15(A12)Trp->Arg ELECTROPHORESIS Hb FX moves slower than Hb F (between Hb S and Hb C) at alkaline pH IEF Hb FX focuses between Hb S and Hb C CHROMATOGRAPHY Hb FX can readily be separated from Hb A and Hb F by DEAE-cellulose chromatography CHAIN SEPARATION GgammaX = 36.8%; Ggamma = 35.4%; Agamma = 27.8%; also see NOTES STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation TGG->CGG at codon 15 NOTES Found in two newborn babies from Northern Spain; the sec-ond baby was also an AgammaT heterozygote (Agamma75 Ile->Thr): AgammaT 11.5%; GgammaX 45.5%; Ggamma 31.3%; Agamma 11.7% REFERENCES 1. Plaseska, D., Wilson, J.B., Kutlar, F., Font, Ll., Baiget, M., and Huisman, T.H.J.: Hemoglobin, 14:511, 1990. Hb F-Melbourne Ggamma16(A13)Gly->Arg ELECTROPHORESIS Hb FX moves slower than Hb A and Hb F at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX was isolated by DEAE-cellulose chromatography CHAIN SEPARATION No information STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC at codon 16 NOTES Found in a Spanish baby living in Australia; quantity in the heterozygote: 26% of total Hb; 29% of total Hb F REFERENCES 1. Brennan, S.O., Smith, M.B., and Carrell, R.W.: Biochim. Biophys. Acta, 490:452, 1977. Hb F-Fuchu Ggamma21(B3)Glu->Gln ELECTROPHORESIS Not reported; sample was collected on filter paper IEF Hb FX moves slower than Hb F and Hb A CHROMATOGRAPHY Not reported CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion; mass spectrometric analysis DNA ANALYSES Not reported; presumed mutation GAA->CAA at codon 21 NOTES Found in four Japanese newborns in Osaka REFERENCES 1. Wada, Y., Fujita, T., Kidoguchi, K., and Hayashi, A.: Hum. Genet., 72:196, 1986. Hb F-Saskatoon Ggamma21(B3)Glu->Lys ELECTROPHORESIS Hb FX moves slower than Hb F at alkaline pH IEF Hb FX focuses between Hb A2 and Hb A2' CHROMATOGRAPHY Hb FX separates from Hb F and Hb A CHAIN SEPARATION Not reported STRUCTURE STUDIES Not done DNA ANALYSES A GAA->AAA mutation at codon 21 NOTES Found in an American Indian baby; quantity in the heterozygote 16.2% of total Hb; 23.3% of total Hb F REFERENCES 1. Pobedimskaya, D.D., Molchanova, T.P., Huisman. T.H.J., Harding, S.R., and Bakanec, R.: Hemoglobin, 17:547, 1993. Hb F-Urumqi Ggamma22(B4)Asp->Gly ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->GGT at codon 22 NOTES Found in a Chinese newborn (Uygur parentage); Hb FX 21.5% of total Hb REFERENCES 1. Hu, H. and Ma, M.: Hemoglobin, 10:15, 1986. Hb F-Granada Ggamma22(B4)Asp->Val ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAT->GTT at codon 22 NOTES Found in a Spanish newborn; Hb FX 22% of total Hb REFERENCES 1. de Pablos, J.Ma. and Clegg, J.B.: Hemoglobin, 12:405, 1988. Hb F-Cosenza Ggamma25(B7)Gly->Glu ELECTROPHORESIS Hb FX moves faster than Hb A at alkaline pH IEF Hb FX focuses faster than Hb A CHROMATOGRAPHY Not reported CHAIN SEPARATION GgammaX = 23.4%; Ggamma = 41.6%; Agamma = 35% STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGA->GAA at codon 25 NOTES Found in an Italian newborn; Hb FX 22.4% of total Hb REFERENCES 1. Qualtieri, A., Crescibene, L., Bagala, A., De Marco, E.V., Bria, M., and Brancati, C.: Hemoglobin, 15:509, 1991. Hb F-Oakland Ggamma26(B8)Glu->Lys ELECTROPHORESIS Hb FX moves slightly slower than Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes from a cation exchange HPLC column behind Hb A CHAIN SEPARATION GgammaX = 32.1%; Ggamma = 40.4%; Agamma = 27.5% STRUCTURE STUDIES Digestion of gammaX chain with trypsin; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAA->AAA at codon 26 NOTES Found in a newborn of Chinese-Black descent; Hb FX 32% of total Hb REFERENCES 1. Kleman, K., Lubin, B., Wilson, J.B., Kutlar, A., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 11:181, 1987. Hb F-Tokyo Ggamma34(B16)Val->Ile ELECTROPHORESIS No separation observed IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION GgammaX = 31.3%; Ggamma = 34.4%; Agamma = 34.4% STRUCTURE STUDIES Isolation of GgammaX by preparative reversed phase HPLC; tryptic digestion; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GTC->ATC at codon 34 NOTES Found in a Japanese newborn REFERENCES 1. Chen, S.S., Wilson, J.B., Webber, B.B., Huisman, T.H.J., Miwa, S., and Amenomori, Y.: Hemoglobin, 9:25, 1985. Hb F-Austell Ggamma40(C6)Arg->Lys ELECTROPHORESIS Hb FX moves slightly slower than Hb F at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX elutes slightly faster than Hb F in cation exchange HPLC CHAIN SEPARATION AgammaT = 15%; Ggamma+GgammaX = 73.4%; Agamma = 11.6% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGG->AAG at codon 40 NOTES Found in a Black newborn; baby was also heterozygous for the AgammaT chain; Hb FX 27% of total Hb REFERENCES 1. Kutlar, A., Kutlar, F., Wilson, J.B., Webber, B.B., Hu, H., and Huisman, T.H.J.: Hemoglobin, 12:409, 1988. Hb F-Veleta Ggamma40(C6)Arg->Gly ELECTROPHORESIS Hb FX separates well from Hb A and Hb F; Hb X moves between Hb A and Hb F IEF Hb FX focuses between Hb A and Hb A1 CHROMATOGRAPHY Hb FX elutes ahead of Hb F1 and Hb FO by cation exchange HPLC CHAIN SEPARATION AgammaT = 14.1%; GgammaX = 33.4%; Ggamma = 35.5%; Agamma = 17% STRUCTURE STUDIES Not reported DNA ANALYSES An AGG->GGG mutation at codon 40 NOTES Found in a Spanish newborn, who was also heterozygous for the AgammaT chain; family studies indicated that both mutations occur on the same chromosome (Agamma*Ggamma*/AgammaT*GgammaX*) REFERENCES 1. de Pablos Gallego, J.Ma., Gu, L-H., Leonova, J.Ye., and Huisman, T.H.J.: Hemo-globin, 19:407, 1995. Hb F-Cincinnati Ggamma41(C7)Phe->Ser ELECTROPHORESIS Hb FX did not separate from Hb F at alkaline pH IEF Hb FX did not separate from Hb F by IEF CHROMATOGRAPHY Not reported CHAIN SEPARATION GgammaX = 29.5%; Ggamma = 37%; Agamma = 33.5% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES A TTC->TCC mutation at codon 41 NOTES Found in a Caucasian newborn with cyanosis; baby became normal when Hb F disappeared after birth REFERENCES 1. Kholi-Kumar, M., Zwerdling, T., and Rucknagel, D.L.: Am. J. Hematol., 49:43, 1995. Hb F-Lodz Ggamma44(CD3)Ser->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Same as above CHROMATOGRAPHY Not reported CHAIN SEPARATION GgammaX+AgammaT = 61.2%; Ggamma = 25.6%; Agamma = 13.2% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AGC->CGC at codon 44 NOTES Found in a Polish newborn; Hb FX 37.1% of total Hb REFERENCES 1. Honig, G.R., Koshy, M., Schroeder, W.A., Shelton, J.B., and Shelton, J.R.: Biochim. Biophys. Acta, 707:213, 1982. 2. Cepreganova, B., Gu, L-H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 15: 549, 1991. Hb F-Kingston Ggamma55(D6)Met->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX can be isolated by DEAE-cellulose chromatography CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation ATG->AGG at codon 55 NOTES Found in a Jamaican baby and a Spanish baby; Hb FX 21% of total Hb REFERENCES 1. Serjeant, G.R., Serjeant, B.E., Lehmann, H., Dukes, M., and Robb, L.: FEBS Lett., 150:77, 1982. 2. de Pablos, J.Ma., Wilson, J.B., Kutlar, A., Kutlar, F., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 11:513, 1987. Hb F-Sacromonte Ggamma59(E3)Lys->Gln ALSO KNOWN AS F-Foch ELECTROPHORESIS Hb FX moves faster than Hb A at alkaline pH IEF Same results CHROMATOGRAPHY No separation by cation exchange HPLC CHAIN SEPARATION GgammaX = 31% of total gamma; AgammaT = 16.4%; Ggamma = 31.5%; Agamma = 21.1% STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES An AAA->CAA mutation at codon 59 NOTES Found in a Spanish newborn, and in a French baby; Hb FX 25% of total Hb REFERENCES 1. Pobedimskaya, D.D., Molchanova, T.P., Gu, L-H., Molina, M.A., de Pablos, J.Ma., and Huisman, T.H.J.: Hemoglobin, 17:269, 1993. 2. Abbes, S., Fitzgerald, P.A., Varady, E., Girot, R., Pic, P., Blouquit, Y., Ducrocq, R., Drupt, F., and Wajcman, H.: Hemoglobin, 19:173, 1995. Hb F-Emirates Ggamma59(E3)Lys->Glu ELECTROPHORESIS Not reported IEF Hb FX moves faster than Hb A CHROMATOGRAPHY Not reported CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis (no differentiation made between Glu and Gln) DNA ANALYSES Not reported; presumed mutation AAA->GAA at codon 59 NOTES Found in an Arabian baby; Hb FX ~37% of total Hb REFERENCES 1. Abbes, S., Fitzgerald, P.A., Varady, E., Girot, R., Pic, P., Blouquit, Y., Ducrocq, R., Drupt, F., and Wajcman, H.: Hemoglobin, 19:173, 1995. Hb F-M-Osaka Ggamma63(E7)His->Tyr ELECTROPHORESIS No variant detectable IEF No variant detectable CHROMATOGRAPHY A broad Hb FX band elutes ahead of Hb A and Hb F on DEAE-cellulose chromatography CHAIN SEPARATION GgammaX = 17.5% of total gamma; Ggamma = 40%; Agamma = 42.5% STRUCTURE STUDIES Tryptic digestion of GgammaX; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAT->TAT at codon 63 NOTES Found in a Japanese newborn and a Caucasian newborn; variant has a decreased oxygen affinity, increased Bohr effect; babies are cyanotic at birth; methemoglobinemia REFERENCES 1. Hayashi, A., Fujita, T., Fujimura, M., and Titani, K.: Hemoglobin 4:447, 1980. 2. Glader, B.E., Zwerdling, D., Kutlar, F., Kutlar, A., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 13:769, 1989. Hb F-Clarke Ggamma65(E9)Lys->Asn ELECTROPHORESIS Hb FX moves slightly faster than Hb A at alkaline pH IEF Same as above CHROMATOGRAPHY Hb FX elutes slightly ahead of Hb F in cation exchange HPLC CHAIN SEPARATION GgammaX = 36.4% of total gamma; Ggamma = 33.4%; Agamma = 30.2% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->AAT or AAC at codon 65 NOTES Found in a newborn of Hispanic descent REFERENCES 1. Kutlar, A., Kutlar, F., Wilson, J.B., Webber, B.B., Gonzalez Redondo, J.M., and Huisman, T.H.J.: Hemoglobin, 11:185, 1987. Hb F-Shanghai Ggamma66(E10)Lys->Arg ELECTROPHORESIS No separation reported IEF No separation reported CHROMATOGRAPHY Not reported; no separation by DEAE-cellulose chromatography CHAIN SEPARATION GgammaX = 35.5% of total gamma; Ggamma = 37.9%; Agamma = 26.6% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAG->AGG at codon 66 NOTES Found in a Chinese newborn REFERENCES 1. Zeng, Y-T., Huang, S-Z., Nakatsuji, T., and Huisman, T.H.J.: Am. J. Hematol., 18: 235, 1985. Hb F-Brooklyn Ggamma66(E10)Lys->Gln ELECTROPHORESIS Hb FX moves slightly faster than Hb A at alkaline pH IEF About the same CHROMATOGRAPHY Hb FX can be separated from Hb A and Hb F by cation exchange HPLC CHAIN SEPARATION GgammaX = 25.1% of total gamma; Ggamma = 39.3%; Agamma = 35.6% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation AAG->CAG at codon 66 NOTES Found in a Caucasian newborn; Hb FX 23% of total Hb REFERENCES 1. Plaseska, D., Li, H-J., Wilson, J.B., Kutlar, F., Kutlar, A., Huisman, T.H.J., and Kulpa, J.: Hemoglobin, 14:213, 1990. Hb F-Minoo Ggamma72(E16)Gly->Arg ELECTROPHORESIS No data presented IEF Hb FX moves between Hb S and Hb C CHROMATOGRAPHY No data presented CHAIN SEPARATION No data given STRUCTURE STUDIES No details provided DNA ANALYSES Not done; presumed mutation GGA->CGA at codon 72 NOTES Found in a Japanese baby REFERENCES 1. Wada, Y., Fujita, T., Kidoguchi, K., and Hayashi, A.; Hum. Genet., 72:196, 1986. Hb F-Kennestone Ggamma77(EF1)His->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX can be isolated by DEAE-cellulose chromatography CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CGC at codon 77 NOTES Found in a Caucasian newborn; quantity in the heterozygote: 25.3% of total Hb or 30.7% of total Hb F REFERENCES 1. Nakatsuji, T., Lam, H., and Huisman, T.H.J.: Hemoglobin, 7:267, 1983. Hb F-Marietta Ggamma80(EF4)Asp->Asn ELECTROPHORESIS Hb FX moves slightly slower than Hb S IEF Not reported CHROMATOGRAPHY Hb FX elutes ahead of Hb F on a DEAE-cellulose column CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 80 NOTES Found in a Caucasian baby; Hb FX 12.4% of total Hb and 16.2% of total Hb F REFERENCES 1. Nakatsuji, T., Lam, H., Carver, J., and Huisman, T.H.J.: Hemoglobin, 6:407, 1982. Hb F-M-Fort Ripley Ggamma92(F8)His->Tyr ELECTROPHORESIS No separation observed IEF No separation observed CHROMATOGRAPHY No separation observed CHAIN SEPARATION GgammaX = 12.4% of total gamma; AgammaT = 22.7%; Ggamma = 45.1%; Agamma = 19.8% STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES A CAC->TAC mutation at codon 92 (Ref. 3) NOTES Found in an American and a Canadian newborn; neonatal cyanosis; spectral changes are described in Ref. 3; slightly increased oxygen affinity REFERENCES 1. Priest, J.R., Watterson, J., Jones, R.T. Faassen, A.E., and Hedlund, B.E.: Pediatrics, 83:734, 1989. 2. Glader, B.E.: Pediatrics, 83:792, 1989. 3. Molchanova, T.P., Wilson, J.B., Gu, L-H., Hain, R.D.W., Chang, L.S., Poon, A.O., and Huisman, T.H.J.: Hemoglobin, 16:389, 1992. Hb F-Columbus-GA Ggamma94(FG1)Asp->Asn ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX was isolated by DEAE-cellulose chromatography CHAIN SEPARATION GgammaX = 39% of total gamma; Ggamma = 37%; Agamma = 24% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAC->AAC at codon 94 NOTES Found in a Caucasian baby; Hb FX 30.5% of total Hb REFERENCES 1. Nakatsuji, T., Lam, H., Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 6:593, 1982. Hb F-La Grange Ggamma101(G3)Glu->Lys ELECTROPHORESIS Hb FX moves slightly faster than Hb S IEF Not reported CHROMATOGRAPHY Hb FX can readily be isolated by DEAE-cellulose chromatography CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->AAG at codon 101 NOTES Found in a Caucasian newborn; Hb FX 14% of total Hb; variant forms hybrid Hbs with Hb F or Hb A; mildly unstable; increased oxygen affinity; lower heme-heme interaction REFERENCES 1. Nakatsuji, T., Shimizu, K., and Huisman, T.H.J.: Biochim. Biophys. Acta, 789:224, 1984. Hb F-Macedonia-II Ggamma104(G6)Lys->Asn ELECTROPHORESIS No separation reported at alkaline pH (Hb FX apparently takes the position of Hb A) IEF Not data reported CHROMATOGRAPHY No data reported CHAIN SEPARATION GgammaX = 32.4% of total gamma; Ggamma = 32.8%; Agamma = 34.8% STRUCTURE STUDIES Not done DNA ANALYSES An AAG->AAC mutation at codon 104; G is part of the donor splice site of the second intron; substitution by C may not have altered splicing of the mRNA NOTES Found in a Macedonian baby REFERENCES 1. Plaseska, D., Panovska-Popovska, S., Lazarevski, M., and Efremov, G.D.: Hemoglobin, 18:373, 1994. Hb F-Malta-I Ggamma117(G19)His->Arg ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF About the same CHROMATOGRAPHY Hb FX can be separated from Hb A and Hb F by cation and anion exchange chromatography CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of AE-gammaX chain; separation of peptides by fingerprinting and reversed phase HPLC; amino acid analysis DNA ANALYSES A CAT->CGT mutation at codon 117 (Ref. 3) NOTES Occurs at reasonably high frequency in Maltese and some Italian newborn babies; its occurrence is linked to the beta chain variant Hb Valletta [beta87(F3)Thr->Pro] (Ref. 3) REFERENCES 1. Cauchi, M.N., Clegg, J.B., and Weatherall, D.J.: Nature, 223:311, 1969. 2. Altay, G., Garver, F., Bannister, W.H., Grech, J.L., Felice, A.E., and Huisman, T.H.J.: Biochem. Genet., 15:915, 1977. 3. Kutlar, F., Felice, A.E., Grech, J.L., Bannister, W.H., Kutlar, A., Wilson, J.B., Webber, B.B., Hu, H., and Huisman, T.H.J.: Hum. Genet., 86:591, 1991. Hb F-Caltech Ggamma120(GH3)Lys->Gln ELECTROPHORESIS Hb FX moves faster than Hb A IEF Not reported CHROMATOGRAPHY Hb FX can be isolated by DEAE- and CM-cellulose chromatography CHAIN SEPARATION AgammaT = 14%; GgammaX = 31%; Ggamma = 41%; Agamma = 14% STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation AAA->CAA at codon 120 NOTES Found in an infant of French-Swedish-Hispanic extraction; the baby was also heterozygous for the AgammaT chain REFERENCES 1. Shelton, J.B., Shelton, J.R., Espinueva, Z., Huynh, V., Schroeder, W.A., and Powars, D.: Hemoglobin, 6:577, 1982. Hb F-Carlton Ggamma121(GH4)Glu->Lys ELECTROPHORESIS Hb FX moves slower than Hb C at alkaline pH IEF About the same CHROMATOGRAPHY Hb FX can be separated from Hb A and Hb F by DEAE-cellulose chromatography CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of isolated gammaX chain; separation of pep-tides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAA->AAA at codon 121 NOTES Found in a newborn of Italian parentage; Hb FX 26% of total Hb F REFERENCES 1. Brennan, S.O., Smith, M.B., and Carrell, R.W.: Biochim. Biophys. Acta, 490:452, 1977. Hb F-Port Royal Ggamma125(H3)Glu->Ala ELECTROPHORESIS Hb FX moves between Hb S and Hb C IEF The same CHROMATOGRAPHY Hb FX can be separated by cation and anion exchange HPLC CHAIN SEPARATION STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by cation exchange HPLC; amino acid analysis; glycinamida-tion; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GCG at codon 125 NOTES Found in Black babies; associated with the Ggamma-Ggamma arrangement; quantity of Hb FX 14-16% of total Hb F REFERENCES 1. Brimhall, B., Vedvick, T.S., Jones, R.T., Ahern, E., Palomino, E., and Ahern, V.: Br. J. Haematol., 27:313, 1974. 2. Huisman, T.H.J.: Personal communication, 1983. Hb F-Poole Ggamma130(H8)Trp->Gly ELECTROPHORESIS No separation observed at alkaline pH IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation TGG->GGG at codon 130 NOTES Found in a Black-Caucasian baby living in Poole, Dorset, England; variant is unstable; baby had hemolytic anemia REFERENCES 1. Lee-Potter, J.P., Deacon-Smith, R.A., Simpkiss, M.J., Kamuzora, H., and Leh-mann, H.: J. Clin. Pathol., 28:317, 1975. Hb F-Onoda Ggamma146(HC3)His->Tyr ELECTROPHORESIS Not reported IEF Hb FX moves between Hb F and Hb A CHROMATOGRAPHY Not reported CHAIN SEPARATION GgammaX = 35.9%; Ggamma = 33.5%; Agamma = 30.6% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting; amino acid analysis; carboxypeptidase A DNA ANALYSES Not reported; presumed mutation CAC->TAC at codon 146 NOTES Found in a Japanese baby; Hb FX 26.4% of total Hb or 35% of total Hb F; increased oxygen affinity; normal Bohr effect and cooperativity REFERENCES Hb Lepore-Hollandia deltabeta hybrid (delta through 22; beta from 50) HEMATOLOGY Mild anemia with microcytosis and hypochromia in the heterozygote (beta+-thal) ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH CHROMATOGRAPHY Hb X and Hb A can be separated by CM-cellulose or DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES A large deletion was observed by gene mapping FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect and cooperativity STABILITY Stable OCCURRENCE Found in several Papuan families OTHER INFORMATION Quantity in the heterozygote 12%; in the homozygote 26% REFERENCES 1. Barnabas, J. and Muller, C.J.: Nature, 194:931, 1962. 2. Curtain, C.C.: Austrl. J. Exper. Biol. Med. Sci., 42:89, 1964. 3. McDonald, M.J., Noble, R.W., Sharma, V.S., Ranney, H.M., Crookston, J.H., and Schwartz, J.M.: J. Mol. Biol., 94:305, 1975. Hb Lepore-Baltimore deltabeta hybrid (delta through 50; beta from 86) HEMATOLOGY Mild anemia with microcytosis and hypochromia in the heterozygote (beta+-thal) ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH and by IEF CHROMATOGRAPHY Hb X and Hb A can be separated on a DEAE-Sephadex column; Hb X elutes between Hb A and Hb A2 by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of deltabeta chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES A large deletion was observed by gene mapping FUNCTION STUDIES Not reported STABILITY Stable OCCURRENCE Found mainly in Spanish families; also in an individual of African ancestry, and in four members in three generations of a Yugoslavian family OTHER INFORMATION Quantity in heterozygotes 7.1-15%; in homozygotes 30% REFERENCES 1. Ostertag, W. and Smith, E.W.: Eur. J. Biochem., 10:371, 1969. 2. Efremov, G.D., Rudivic, R., Niazi, G.A., Hunter, E., Huisman, T.H.J., and Schroeder, W.A.: Scand. J. Haematol., 16:81, 1976. 3. Villegas, A., Espinos, D., Alvarez-Sala, J.L., Calero, F., Valverde, F., Robb, L., and Lehmann, H.: Acta Haematol., 69:192, 1983. Hb Lepore-Boston-Washington deltabeta hybrid (delta through 87; beta from 116) HEMATOLOGY Mild anemia with microcytosis and hypochromia in the heterozygote (beta+-thal) ELECTROPHORESIS Hb X and Hb A can be separated by standard procedures at alkaline pH; Hb X moves to the position of Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by cation and anion exchange chromatography; it elutes between Hb A and Hb A2 in cation exchange HPLC STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES A large deletion was observed by gene mapping FUNCTION STUDIES Not reported STABILITY Stable OCCURRENCE Hb Lepore-B-W is the most common Hb Lepore type; found mainly in Italian families; it has also been observed in families from Rumania, Yugoslavia, Turkey, Cyprus, Jamaica, Cuba, Greece, England, Australia, Mexico, etc. OTHER INFORMATION Quantity in heterozygotes 7-13%; found in combination with Hb S, Hb C, beta+-thal, and in the homozygous state REFERENCES 1. Baglioni, C.: Proc. Natl. Acad. Sci. USA, 48:1880, 1962. 2. Labie, D., Schroeder, W.A., and Huisman, T.H.J.: Biochim. Biophys. Acta, 127: 428, 1966. 3. And numerous others. The reader is invited to consult text books such as: Bunn and Forget, Hemoglobin: Molecular, Genetic and Clinical Aspects, Saunders, Philadelphia, 1986; Weatherall and Higgs, The Haemoglobinopathies, Bailliere's Clinical Haematology, Vol. 6, Saunders, London, 1993. Hb Parchman Two crossovers have been described: a) deltabeta hybrid (delta through 12; beta from 22); b) betadelta hybrid (beta from 22 through 50; delta from 87) HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves like Hb S at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Gene mapping identified a deltabetadelta gene FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a Black male living in Mississippi OTHER INFORMATION Quantity in the heterozygote 1.6%; found in a patient who was heterozygous for alpha-thal-2 REFERENCES 1. Adams, J.G., III, Morrison, W.T., and Steinberg, M.H.: Science, 218:291, 1982. Hb Miyada betadelta hybrid (beta through 12; delta from 22) HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves like Hb A2 at alkaline pH CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Gene mapping has identified this betadelta hybrid to be located between a delta and a beta gene; the hybrid gene results from a non-homologous crossover between beta and delta genes FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Japanese family and in a 24-year-old Italian male OTHER INFORMATION Quantity in heterozygotes 17%; found in association with beta+-thal REFERENCES 1. Yanase, T., Hanada, M., Seita, M., Ohya, I., Ohta, Y., Imamura, T., Fujimura, T., Kawasaki, K., and Yamaoka, K.: Jpn. J. Hum. Genet., 13:40, 1968. 2. Ohta, Y., Yamaoka, K., Sumida, I., and Yanase, T.: Nature, 234:218, 1971. 3. Roberts, A.V., Clegg, J.B., Weatherall, D.J., and Ohta, Y.: Nature, 245:23, 1973. 4. Driscoll, M.C., Baird, M., Ohta, Y., and Bank, A.: Blood, 58:53a (Suppl. 1), 1981. Hb P-Congo betadelta hybrid (beta through 22; delta from 116) HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to the position of Hb S at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; it may be that the betadelta gene of Hb P-Congo is located between a delta and a beta gene; the hybrid gene may result from a non-homologous crossover between beta and delta genes FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in several families from the Congo OTHER INFORMATION Found in combination with Hb S REFERENCES 1. Lehmann, H. and Charlesworth, D.: Biochem. J., 119:43, 1970. 2. Dherte, P., Lehmann, H., and Vandepitte, J.: Nature, 184:1133, 1975. Hb P-Nilotic betadelta hybrid (beta through 22; delta from 50) HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slower than Hb A at alkaline pH; it separates readily by IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex or DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion of AE-deltabeta chain; separation of peptides by fingerprinting, cation exchange chromatography or reversed phase HPLC; amino acid analysis DNA ANALYSES The betadelta gene of Hb P-Nilotic is located between a delta and a beta gene and results from a non-homologous crossover between beta and delta genes; this crossover occurred without loss of bases within a 54 bp stretch of DNA between nts 275 and 330 (corresponding to amino acid residues 31 and 50); thus, exon 1 and IVS-I originate from beta; exon 2, IVS-II, and exon 3 from delta FUNCTION STUDIES Increased oxygen affinity; normal Bohr effect and cooperativity STABILITY Normal OCCURRENCE Found in a Nubian living in Cairo, and in Mexican-American, Turkish, and Sudanese families OTHER INFORMATION Quantity in the heterozygote 16-21%; found in association with beta+-thal REFERENCES 1. Badr, F.M., Lorkin, P.A., and Lehmann, H.: Nature, 242:107, 1973. 2. Moo-Penn, W.F., Bechtel, K.C., and Therrell, B.L.: Hemoglobin, 2:65, 1978. 3. Raybourne, S.R. Stallings, M.B., Gravely, M.E., and Huisman, T.H.J.: Biochim. Biophys. Acta, 535:78, 1978. 4. Abu-Sin, A., Felice, A.E., Gravely, M.E., Wilson, J.B., Reese, A.L., Lam, H., Miller, A., and Huisman, T.H.J.: J. Lab. Clin. Med., 93:973, 1979. 5. Altay, C., Kutlar, A., Wilson, J.B., Webber, B.B., and Huisman, T.H.J.: Hemoglobin, 11: 395, 1987. 6. Liu, J-Z., Harano, T., Lanclos, K.D., and Huisman, T.H.J.: Biochim. Biophys. Acta, 909: 208, 1987. Hb Lincoln Park betadelta hybrid (beta through 22; delta from 50)as in Hb P-Nilotic but with the deletion of a valine residue at delta137 HEMATOLOGY Mild hemolytic anemia; reticulocytosis ELECTROPHORESIS Hb X moves slightly faster than Hb S at alkaline pH; and by IEF CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion of AE-betadelta chain; separation of peptides by cation exchange chromatography; amino acid analysis; Edman PTH degradation DNA ANALYSES Not reported; presumably a P-Nilotic betadelta gene with an additional deletion of a GTG triplet at codon 137 FUNCTION STUDIES Normal oxygen affinity STABILITY Normal OCCURRENCE Found in members of a family in Southern Mexico OTHER INFORMATION Quantity in the heterozygote 14%; decreased globin chain synthesis in reticulocytosis REFERENCES 1. Honig, G.R., Shamsuddin, M., Mason, R.G., and Vida, L.N.: Proc. Natl. Acad. Sci. USA, 75:1475, 1978. 2. Honig, G.R., Mason, R.G., Tremaine, L.M., and Vida, L.N.: Am. J. Hematol., 5:335, 1978. Hb P-India betadelta hybrid (beta through 87; delta from 116) HEMATOLOGY Not known; carriers had nutritional anemia and an alpha-thal-2 heterozygosity ELECTROPHORESIS Not reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Peptide separation; amino acid analysis DNA ANALYSES Recombination point is located between beta codon 87 and the 8th nt of the delta gene; nearly the entire IVS-II is delta type FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in an Indian family OTHER INFORMATION Quantity in the heterozygote 23% REFERENCES 1. Prehu, M-O., Prehu, C., Goossens, M., Galacteros, F., and Wajcman, H.: Blood, 83:261a (Suppl. 1), 1994. Hb Kenya Agammabeta hybrid (Agamma through 81; beta from 86) HEMATOLOGY Normal in the heterozygote; elevation of Hb F (Ggamma Hb F) ELECTROPHORESIS Hb X moves slightly slower than Hb S at alkaline pH; about the same by IEF CHROMATOGRAPHY Hb X was isolated on DEAE-Sephadex or Amberlite IRC-50 columns STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography or fingerprinting; amino acid analysis DNA ANALYSES Gene mapping has identified the expected 22.5 kb deletion FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in several families from Kenya, Uganda, and other countries near Lake Victoria in Africa OTHER INFORMATION Quantity in the heterozygote 6%; with Hb S 16-22%; found in combination with Hb S and Hb A2'; homogeneous distribution of Hb F in red cells REFERENCES 1. Huisman, T.H.J., Wrightstone, R.N., Wilson, J.B., Schroeder, W.A., and Kendall, A.G.: Arch. Biochem. Biophys., 153:850, 1972. 2. Kendall, A.G., Ojwang, P.J., Schroeder, W.A., and Huisman, T.H.J.: Am. J. Hum. Genet., 25:548, 1973. 3. Smith, D.H., Clegg, J.B., Weatherall, D.J., and Gilles, H.M.: Nature, 246:184, 1973. 4. Kendall, A.G. and Ojwang, P.J.; E. Afr. Med. J., 51:434, 1974. 5. Nute, P.E., Wood, W.G., Stamatoyannopoulos, G., Olweny, C., and Failkow, P.J.: Br. J. Haematol., 32:55, 1976. 6. Ojwang, P.J., Nakatsuji, T., Gardiner, M.B., Reese, A.L., Gilman, J.G., and Huis-man, T.H.J.: Hemoglobin, 7:115, 1983. Hb Catonsville Glu- inserted between alpha37(C2)Pro and alpha38(C3)Thr HEMATOLOGY Mild erythrocytosis; reticulocytosis; hemolytic episodes ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH; at acidic pH Hb X moves between Hb A and Hb F CHROMATOGRAPHY Hb X elutes faster than Hb A from a cation exchange HPLC column; no resolution of chains (alphaX and alphaA) by reversed phase HPLC STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Insertion of GAA between CCC [codon 37 (= Pro)] and ACC [codon 38 (= Thr)] FUNCTION STUDIES Increased oxygen affinity; reduced cooperativity and Bohr effect STABILITY Unstable OCCURRENCE Found in a young child and his father OTHER INFORMATION Quantity in the heterozygote 24.2% REFERENCES 1. Moo-Penn, W.F., Swan, D.C., Hine, T.K., Baine, R.M., Jue, D.L., Benson, J.M., Johnson, M.H., Virshup, D.M., and Zinkham, W.H.: J. Biol. Chem., 264:21454, 1989. Hb Zaire His-Leu-Pro-Ala-Glu- inserted between alpha116(GH4)Glu and alpha117(GH5)Phe HEMATOLOGY Normal; slight microcytosis and hypochromia in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; frameshift is suggested FUNCTION STUDIES Normal STABILITY Normal OCCURRENCE Found in a 36-year-old Zairian patient OTHER INFORMATION Hb X 19% in the heterozygote; Hb X2 0.4% REFERENCES 1. Wajcman, H., Blouquit, Y., Vasseur, C., Le Querrec, A., Laniece, M., Melevendi, C., Rasore, A., and Galacteros, F.: Hum. Genet., 89:676, 1992. Hb Grady Glu-Phe-Thr- inserted between alpha118(H1)Thr and alpha119(H2)Pro ALSO KNOWN AS Dakar HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH CHROMATOGRAPHY Hb X was isolated by DEAE-Sephadex and DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion; separation of peptides by cation exchange chromatography or fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; mismatched intragenic crossover suggested FUNCTION STUDIES Nearly normal oxygen affinity; Bohr effect and cooperativity normal STABILITY Unstable OCCURRENCE Found in a few Black families OTHER INFORMATION Quantity in the heterozygote 8%; found in association with alpha-thal REFERENCES 1. Huisman, T.H.J., Wilson, J.B., Gravely, M., and Hubbard, M.: Proc. Natl. Acad. Sci. USA, 71:3270, 1974. 2. Huisman, T.H.J. and Miller, A.: Am. J. Hum. Genet., 28:363, 1976. 3. Garel, M.C., Goossens, M., Oudart, J.L., Blouquit, Y., Thillet, J., and Rosa, J.: Biochim. Biophys. Acta, 453:459, 1976. 4. Scott, A.F., Phillips, J.A., III, Young, K.E., Kazazian, H.H., Jr., Smith, K.D., Charache, S., and Clegg, J.B.: Am. J. Hum. Genet., 33:129, 1981. 5. Cleek, M.P., Gardiner, M.B., Reese, A.L., Harris, H.F., Felice, A.E., and Huisman, T.H.J.: Am. J. Hum. Genet., 35:1314, 1983. Hb Koriyama Leu-His-Cys-Asp-Lys- inserted between beta95(FG2)Lys and beta96(FG3)Leu HEMATOLOGY Severe chronic hemolytic anemia; blood transfusion dependent; splenectomized; reticulocytosis ELECTROPHORESIS Minor band (1.5%) near Hb A in cellulose acetate electrophoresis; a minor band near Hb F in IEF; data not very reproducible CHROMATOGRAPHY Minor betaX chain elutes behind betaA in CM-cellulose chromatography (reticulocytes incubated with 3H-leucine; betaX identified as a minor zone with high activity) STRUCTURE STUDIES Tryptic digestion of AE-betaX chain (radioactive); separation of peptides by reversed phase HPLC; amino acid analysis; radio sequencing DNA ANALYSES Not reported; frameshift mutagenesis is suggested FUNCTION STUDIES Not possible STABILITY Severely unstable OCCURRENCE Found in a Japanese girl, but her parents are normal OTHER INFORMATION The insertion is identical to the deletion seen in Hb Gun Hill; it is referred to as the anti-Gun Hill insertion REFERENCES 1. Kawata, R., Ohba, Y., Yamamoto, K., Miyaji, T., Makita, R., Ohga, K., Watanabe, S., and Miwa, S.: Hemoglobin, 12:311, 1988 Hb Montreal Deletion of Asp-Gly-Leu- at beta73, beta74, beta75; insertion of Ala-Arg-Cys-Gln- HEMATOLOGY Moderately severe hemolytic anemia; Heinz bodies; reticulocytosis ELECTROPHORESIS Hb X moves like Hb D in IEF CHROMATOGRAPHY Hb X elutes much slower than Hb A2 on a cation exchange HPLC column; the betaX chain elutes ahead of betaA (partially separated) on a reversed phase HPLC column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Modified sequence determined between codons 75 and 77 of the beta gene; see original paper for details FUNCTION STUDIES Not done STABILITY Unstable OCCURRENCE Found in a 7-year-old French-Canadian male but not in his parents OTHER INFORMATION Hb X 15-20% of total Hb REFERENCES 1. Plaseska, D., Dimovski, A.J., Wilson, J.B., Webber, B.B., Hume, H.A., and Huisman, T.H.J.: Blood, 77:178, 1991. Hb Galicia Deletion of His-Val- at beta97, beta98; insertion of Leu- HEMATOLOGY Severe hemolytic anemia; reticulocytosis; Heinz bodies ELECTROPHORESIS Hb X moves slightly faster than Hb A2 in IEF CHROMATOGRAPHY Hb X can be isolated by DEAE-cellulose chromatography; the betaX chain separates from the other chains by reversed phase HPLC (elution order: betaA, alpha, betaX, Ggamma, Agamma) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Deletion of ACG at codons 97 and 98 causes removal of His and Val; remaining three nts form codon CTG (= Leu) FUNCTION STUDIES Not done STABILITY Unstable OCCURRENCE Found in a Spanish patient OTHER INFORMATION Quantity in the heterozygote ~26-27% REFERENCES 1. Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., Codrington, J.F., Prchal, J.T., Hall, K.M., de Pablos, J.Ma., Rodriguez, I., and Huisman, T.H.J.: Blood, 75: 1883, 1990. Hb Birmingham Deletion of Leu-Ala-His-Lys- at beta141, beta142, beta143, beta144; insertion of Gln- HEMATOLOGY Hemolytic anemia; reticulocytosis; Heinz bodies ELECTROPHORESIS Hb X moves about like Hb S in cellulose acetate electrophoresis at alkaline pH CHROMATOGRAPHY The betaX chain elutes in two minor zones faster than the betaA chain (reversed phase HPLC) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Deletion of TG*GCC*CAC*A from codons 141 through 144 removes four amino acid residues (Leu, Ala, His, Lys); the remaining triplet CAG codes for glutamine FUNCTION STUDIES Not done STABILITY Unstable OCCURRENCE Found in an adult Black male OTHER INFORMATION Quantity in the heterozygote ~20% REFERENCES 1. Wilson, J.B., Webber, B.B., Hu, H., Kutlar, A., Kutlar, F., Codrington, J.F., Prchal, J.T., Hall, K.M., de Pablos, J.Ma., Rodriguez, I., and Huisman, T.H.J.: Blood, 75: 1883, 1990. Hb J-Singapore alpha78(EF7)Asn->Asp; alpha79(EF8)Ala->Gly CONTACT External; near central cavity HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A separate at alkaline pH; Hb X moves to the position of Hb J CHROMATOGRAPHY Hb X was isolated on a DEAE-Sephadex column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequence analysis DNA ANALYSES Not reported; presumed mutations AAC->GAC and GCG->GGG at codons 78 and 79 (alpha2 or alpha1) FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a Malay family OTHER INFORMATION Quantity in the heterozygote 22-24%; it is possible that this is not a true double variant; the Asn->Asp substitution might be due to deamidation in vivo REFERENCES 1. Blackwell, R.Q., Wong, H.B., Liu, C-S., and Weng, M-I.: Biochim. Biophys. Acta, 278:482, 1972. Hb S-Antilles beta6(A3)Glu->Val; beta23(B5)Val->Ile HEMATOLOGY Mild anemia in the heterozygote; reticulocytosis; ISC; splenomegaly ELECTROPHORESIS Hb X moves slightly slower than Hb S in IEF CHROMATOGRAPHY Hb X and Hb A readily separate by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutations GAG->GTG and GTT->ATT at codons 6 and 23 FUNCTION STUDIES The oxygen affinity of Hb X containing red cells is decreased, particularly when Hb C is also present; Bohr effect is nearly normal STABILITY Hb X gives a strongly positive sickling test OCCURRENCE Found in many members of a family from Martinique, French West Indies OTHER INFORMATION Quantity of Hb X is about that of Hb A in the heterozygote; has occurred in combination with Hb C (causing severe sickle cell syndrome) and with Hb S (severe chronic hemolytic anemia); solubility of deoxyHb X is considerably less than that of Hb S REFERENCES 1. Monplaisir, N., Merault, G., Poyart, C., Rhoda, M-D., Craescu, C., Vidaud, M., Galacteros, F., Blouquit, Y., and Rosa, J.: Proc. Natl. Acad. Sci. USA, 83:9363, 1986. Hb C-Ziquinchor beta6(A3)Glu->Val; beta58(E2)Pro->Arg HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves slightly slower than Hb A2 at alkaline pH; the same is observed in IEF CHROMATOGRAPHY Hb X and Hb A can be separated by DEAE-cellulose or DEAE-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting or cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutations GAG->GTG and CCT->CGT at codons 6 and 58 FUNCTION STUDIES Normal; gelling properties of Hb X are also the same as Hb S STABILITY Tends to become autooxidized OCCURRENCE Found in members of an African family living in Senegal OTHER INFORMATION Quantity in the heterozygote 29-43%; the presence of an alpha-thal allele was not evaluated; the beta58 Pro->Arg mutation is also found in Hb Dhofar REFERENCES 1. Goossens, M., Garel, M.C., Auvinet, J., Basset, P., Ferreira Gomes, P., Rosa, J., and Arous, N.; FEBS Lett., 58:149, 1975. 2. Hassan, W., Basset, P., Oudart, J.L., Goossens, M., and Rosa, J.: Hemoglobin, 1:487, 1977. Hb C-Harlem beta6(A3)Glu->Val; beta73(E17)Asp->Asn HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves like Hb C in standard electrophoresis at alkaline pH; at acidic pH (agar gel) Hb X occupies the position of Hb S CHROMATOGRAPHY Hb X elutes with Hb A2 in anion exchange chromatography; Hb X also separates from Hb A on a CM-Sephadex column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutations GAG->GTG and GAT->AAT at codons 6 and 73 FUNCTION STUDIES Normal STABILITY Hb X is less stable than Hb A and Hb S OCCURRENCE Found in several (10-15) Black families OTHER INFORMATION Quantity in the heterozygote 40-44%; sickling when deoxygenated; when found together with Hb S the condition resembles sickle cell anemia; insoluble in concentrated phosphate; gels at higher concentrations than Hb S; the beta73 Asp->Asn replacement is characteristic for Hb Korle- Bu REFERENCES 1. Bookchin, R.M., Nagel, R.L., and Ranney, H.M.: J. Biol. Chem., 242:248, 1967. 2. Nagel, R.L. and Bookchin, R.M.: Nature, 241:143, 1973. 3. Moo-Penn, W.F., Bechtel, K., Jue, D., Chan, M.S., Hopkins, G., Schneider, N.J., Wright, J., and Schmidt, R.M.: Blood, 46:363, 1975. Hb S-Providence beta6(A3)Glu->Val; beta82(EF6)Lys->Asn->Asp HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A do not separate by routine electrophoresis at either alkaline or acidic pH CHROMATOGRAPHY Not reported; the betaX and betaA chains separate by CM-cellulose chromatog-raphy STRUCTURE STUDIES tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutations GAG->GTG and AAG->AAT or AAC at codons 6 and 82 FUNCTION STUDIES Sickling test is positive; increased oxygen affinity STABILITY Normal OCCURRENCE Found in a West African female OTHER INFORMATION The beta82 position is part of the 2,3-DPG binding site; the beta82 Lys->Asn replacement is characteristic for Hb Providence; both Hb Providence and Hb S-Providence have a tendency to become deamidated REFERENCES 1. Gale, R.E., Blair, N.E., Huehns, E.R., and Clegg, J.B.: Br. J. Haematol., 70:251, 1988. Hb S-Oman beta6(A3)Glu->Val; beta121(GH4)Glu->Lys HEMATOLOGY Presumably normal; the carrier had microcytosis and hypochromia due to a coexisting alpha-thal-2 homozygosity ELECTROPHORESIS Hb X moves slower than Hb C at alkaline pH CHROMATOGRAPHY Hb X can be separated from Hb A and Hb A2 by anion exchange HPLC STRUCTURE STUDIES Tryptic digestion of Hb X; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->GTG and GAA->AAA at codons 6 and 121 FUNCTION STUDIES Sickling test is positive STABILITY The same as that of Hb S OCCURRENCE Found in a 24-year-old male from Oman OTHER INFORMATION Hb X was 14.5% of total Hb; Hb X is considerably less soluble than Hb S; comparable to Hb S-Antilles; the beta121 Glu-> Lys replacement is characteristic for Hb O-Arab REFERENCES 1. Langdown, J.V., Williamson, D., Knight, C.B., Rubenstein, D., and Carrell, R.W.: Br. J. Haematol., 71:443, 1989. Hb S-Travis beta6(A3)Glu->Val; beta142(H20)Ala->Val HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves to a position between Hb S and Hb F but closer to Hb S at alkaline pH; at acidic pH Hb X moves between Hb A and Hb S CHROMATOGRAPHY Hb X and Hb A can be separated by DEAE-Sephadex chromatography; Hb X elutes immediately before Hb A STRUCTURE STUDIES Tryptic digestion of the betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAG->GTG and GCC->GTC at codons 6 and 142 FUNCTION STUDIES Increased oxygen affinity; decreased affinity for 2,3-DPG and IHP; cooperativity and Bohr effect normal; sickling STABILITY Tends to autooxidize; unstable OCCURRENCE Found in members of a Black family in the USA OTHER INFORMATION Quantity in the heterozygote ~14%; the mean gelling concentration of Hb X is similar to that of Hb S REFERENCES 1. Moo-Penn, W.F., Schmidt, R.M., Jue, D.L., Bechtel, K.C., Wright, J.M., Horne, M.K., Haycraft, G.L., Roth, E.F., and Nagel, R.L.: Eur. J. Biochem., 77:561, 1977. Hb Arlington Park beta6(A3)Glu->Lys; beta95(FG2)Lys->Glu HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A do not separate by standard methodology at both alkaline and acidic pH CHROMATOGRAPHY Not done STRUCTURE STUDIES Tryptic digestion of AE-betaX+betaA chains; separation of peptides by cation exchange chromatography; sequencing DNA ANALYSES Not reported; presumed mutations GAG->AAG and AAG->GAG at codons 6 and 95 FUNCTION STUDIES Not done STABILITY Not reported OCCURRENCE Observed in a 47-year-old Black male suffering from hypertension who died due to a cerebro-vascular accident a few days after admission to hospital; there are no living blood relatives OTHER INFORMATION Accidentally observed when sample was used as a control for peptide mapping; the beta6 Glu->Lys mutation is characteristic for Hb C and beta95 Lys->Glu for Hb N-Baltimore REFERENCES 1. Adams, J.G., III and Heller, P.: Hemoglobin, 1:419, 1977. Hb T-Cambodia beta26(B8)Glu->Lys; beta121(GH4)Glu->Gln OCCURRENCE Found in a Cambodian family OTHER INFORMATION This information was reported to the Repository by Dr. R.C. Barwick; an extended report has not appeared in the literature and no additional information is available; beta26 Glu->Lys is characteristic for Hb E and beta121 Glu->Gln for Hb D-Los Angeles REFERENCES 1. Barwick, R.C., Head, C.G., Shih, M.F-C., Block, S.H., and Jones, R.T.: Blood, 66:68a (Suppl. 1), 1985. Hb Grenoble beta51(D2)Pro->Ser; beta52(D3)Asp->Asn HEMATOLOGY Not presented ELECTROPHORESIS Not detailed CHROMATOGRAPHY No information available STRUCTURE STUDIES Tryptic digestion of Hb X; separation of peptides by reversed phase HPLC; amino acid analysis; mass spectrometry; microsequencing DNA ANALYSES Not reported; presumed mutation CCT->TCT and GAT->AAT at codons 51 and 52 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a French female OTHER INFORMATION The beta52 Asp->Asn mutation is characteristic for Hb Osu-Christiansborg REFERENCES 1. Lacombe, C., Prome, Blouquit, Y., Bardakdjian, J., Arous, N., Mrad, A., Prome, J-C., and Rosa, J.: Hemoglobin, 14:529, 1990. Hb Poissy beta56(D7)Gly->Arg; beta86(F2)Ala->Pro HEMATOLOGY Erythrocytosis in the heterozygote ELECTROPHORESIS Hb X moves like Hb Hamadan at alkaline pH, i.e. slower than Hb A and almost like Hb S CHROMATOGRAPHY Hb X and Hb A separate by DEAE-cellulose chromatography STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by fingerprinting and reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GGC->CGC and GCC->CCC at codons 56 and 86 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and cooperativity STABILITY Mildly unstable; increased autooxidation OCCURRENCE Found in a 56-year-old French male OTHER INFORMATION The beta56 Gly->Arg replacement is found in Hb Hamadan REFERENCES 1. Lacombe, C., Craescu, C.T., Blouquit, Y., Kister, J., Poyart, C., Delanoe-Garin, J., Arous, N., Bardakdjian, J., Riou, J., Rosa, J., Schaeffer, C., and Galacteros, F.: Eur. J. Biochem., 153:655, 1985. Hb Atlanta-Coventry beta75(E19)Leu->Pro; beta141(H19)Leu->0 NOTE: This interesting variant was misidentified and corrected late by the same group of investigators; the leucine residue at position beta141 is not deleted but (partially) oxidized to hydroxyleucine; the same phenomenon has been observed for other Hb Atlanta heterozygotes REFERENCES 1. Brennan, S.O., Williamson, D., Symmans, W.A., and Carrell, R.W.: Hemoglobin, 10:225, 1986. 2. Brennan, S.O., Shaw, J., Allen, J., and George, P.M.: Br. J. Haematol., 81:99, 1992. 3. Brennan, S.O. Shaw, J.G., George, P.M., and Huisman, T.H.J.: Hemoglobin, 17:1, 1993. Hb Villeparisis beta77(EF1)His->Tyr; beta80(EF4)Asn->Ser HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves very close to Hb A at alkaline pH and has a lower pI than Hb A CHROMATOGRAPHY Not reported STRUCTURE STUDIES The betaX and betaA chains separate by reversed phase HPLC; tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; mass spectrometry DNA ANALYSES Not reported; presumed mutations CAC->TAC and AAC->AGC at codons 77 and 80 FUNCTION STUDIES Not reported STABILITY Not reported OCCURRENCE Found in a French male OTHER INFORMATION The beta77 His->Tyr replacement is specific for Hb Fukuyama REFERENCES 1. Wajcman, H., Prome, D., Blouquit, Y., Riou, J., Prehu, C., Bardakdjian, J., and Galacteros, F.: Br. J. Haematol., 87:65 (Suppl. 1), 1994. Hb Duino beta92((F8)His->Pro; beta104(G6)Arg->Ser HEMATOLOGY Hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves slowly at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation CAC->CCC and AGG->AGC or AGT at codons 92 and 104 FUNCTION STUDIES Not reported STABILITY Hb X loses its heme group; heme is only attached to the alpha chain OCCURRENCE Found in an Italian patient OTHER INFORMATION The proband's father was heterozygous for Hb Camper-down (beta104 Arg->Ser) as were three of his brothers; the additional mutation, beta92 His->Pro, also found in Hb Newcastle, must have occurred in the beta-Camperdown gene of the father during spermatogenesis REFERENCES 1. Wajcman, H., Blouquit, Y., Vasseur, C., Le Querrec, A., Laniece, M., Melevendi, C., Rasore, A., and Galacteros, F.: Hum. Genet., 89:676, 1992. Hb Medicine Lake beta98(FG5)Val->Met; beta32(B14)Leu->Gln HEMATOLOGY No data; simple heterozygote not observed ELECTROPHORESIS Not possible CHROMATOGRAPHY Not possible STRUCTURE STUDIES Not possible DNA ANALYSES A CTG->CAG mutation at codon 32 FUNCTION STUDIES Not possible STABILITY Extremely unstable OCCURRENCE Found in a 19-month-old Caucasian female in combination with Hb Koln (beta98 Val->Met; GTG->ATG); both mutations probably occur on the same chromosome OTHER INFORMATION Likely a de novo mutation; the patient had a condition resembling beta-thal major REFERENCES 1. Coleman, M.B., Lu, Z-H., Smith, C.M., II, Adams, J.G., III, Harrell, A., Plonczynski, M., and Steinberg, M.H.: J. Clin. Invest., 95:503, 1995. Hb (no name) beta111(G13)Val->Leu; beta119(GH2)Gly->Asp NOTE: See Hb Fannin-Lubbock or beta119(GH2)Gly->Asp, GGC->GAC REFERENCES 1. Qin, W-B., Pobedimskaya, D.D., Molchanova, T.P., Wilson, J.B., Gu, L-H., de Pablos, J.Ma., and Huisman, T.H.J.: Hemoglobin, 18:297, 1994. Hb Masuda beta114(G16)Leu->Met; beta119(GH2)Gly->Asp HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X and Hb A readily separate by IEF; Hb X focuses ahead of Hb A CHROMATOGRAPHY Hb X elutes ahead of Hb A by cation exchange HPLC STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutations CTG->ATG and GGC->GAC at codons 114 and 119 FUNCTION STUDIES Normal STABILITY Normal to mildly unstable OCCURRENCE Found in a 46-year-old Japanese male OTHER INFORMATION Quantity in the heterozygote estimated at ~40%; the beta114 Leu->Met mutation is characteristic for Hb Zengcheng and beta119 Gly->Asp for Hb Fannin-Lubbock REFERENCES 1. Ohba, Y., Ami, M., Imai, K., Komatsu, K., and Amatsu, K.: Hemoglobin, 13:753, 1989. Hb Cleveland beta121(GH4)Glu->Gln; beta93(F9)Cys->Arg HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X focuses between Hb S and Hb C CHROMATOGRAPHY Hb X elutes more slowly than Hb A2 from a cation exchange column; the betaX chain separates by reversed phase HPLC (elution order: betaX, betaA, delta, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutations GAA->CAA and TGT->CGT at codons 121 and 93 FUNCTION STUDIES Increased oxygen affinity; decreased Bohr effect and heme heme interaction STABILITY Decreased OCCURRENCE Found in an unidentified blood donor, a healthy 26-year-old female OTHER INFORMATION Quantity in the heterozygote ~40%; the beta93 Cys->Arg mutation is characteristic for Hb Okazaki and beta121 Glu->Gln for Hb D-Los Angeles REFERENCES 1. Wilson, J.B., Ramachandran, M., Webber, B.B., Kutlar, F., Hazelwood, L.F., Barnett, D., Hirschler, N.V., and Huisman, T.H.J.: Hemoglobin, 15:269, 1991. Hb F-Texas-II gamma6(A3)Glu->Lys ELECTROPHORESIS Hb FX moves like Hb E at alkaline pH IEF Not reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAG->AAG at codon 6 NOTES Found in a British newborn; quantity in the heterozygote 8% of total Hb REFERENCES 1. Larkin, I.L.M., Baker, T., Lorkin, P.A., Lehmann, H., Black, A.J., and Huntsman, R.G.: Br. J. Haematol., 14:233, 1968. Hb F-Alexandra gamma12(A9)Thr->Lys ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX was isolated by CM-Sephadex chromatography STRUCTURE STUDIES Tryptic digestion of Hb FX; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation ACA->AAA at codon 12 NOTES Found in Greek and Swiss newborn babies REFERENCES 1. Vella, F., Ager, J.A.M., and Lehmann, H.: Nature, 183:30, 1959. 2. Loukopoulos, D., Kaltsoya, A., and Fessas, Ph.: Blood, 33:114, 1969. Hb F-Ube gamma108(G10)Asn->Lys ELECTROPHORESIS No information has been made available except in abstract form DNA ANALYSES Not reported; presumed mutation AAT->AAA at codon 108 NOTES Found in a Japanese baby REFERENCES 1. Omura, H., Miyaji, T., and Shibata, S.: Chem. Abstr., 83:266, 1975. Hb F-Mauritius Agamma23(B5)Ala->Deleted ELECTROPHORESIS Hb FX was isolated from a dried blood spot (collected on paper) IEF Separation by IEF; Hb FX moves slower than Hb F CHROMATOGRAPHY Not performed CHAIN SEPARATION STRUCTURE STUDIES Identified by miniaturized protein chemical procedures, including mass spectrometry DNA ANALYSES DNA was not available NOTES Hb F-Mauritius resembles Hb Freiburg [beta23(B5)Val->deleted] REFERENCES 1. Wajcman, H., Ducrocq, R., Prome, D., and Galacteros, F.: C.R. Acad. Sci. Paris, 318:1065, 1995. Hb F-Xinjiang Agamma25(B7)Gly->Arg; 75(E19)Ile->Thr ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX was isolated by DEAE-cellulose chromatography CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fin-gerprinting; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GGA->CGA at codon 25 NOTES Found in a Chinese newborn of the Han nationality; Hb FX 7.7% of total Hb; the variant is somewhat unstable REFERENCES 1. Hu, H. and Ma, M.; Hemoglobin, 11:465, 1987. Hb F-Fukuyama Agamma43(CD2)Asp->Asn; 75(E19)Ile->Thr ELECTROPHORESIS Not reported IEF Hb FX focuses slower than Hb F but faster than Hb A2 CHROMATOGRAPHY Not reported CHAIN SEPARATION AgammaX = 33.1%; Ggamma = 45.8%; AgammaI = 21.1% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAC->AAC at codon 43 NOTES Found in a Japanese newborn; the authors consider the possibility of an additional gamma-thal to explain the high level of Hb FX (20.6% of total Hb) REFERENCES 1. Hidaka, K., Iuchi, I., Nakahara, H., and Iwakawa, G.: Hemoglobin, 13:93, 1989. Hb F-Forest Park Agamma73(E17)Asp->Asn; 75(E19)Ile->Thr ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF Not reported CHROMATOGRAPHY Hb FX eluted between Hb A2 and Hb A in DEAE-cellulose chromatography CHAIN SEPARATION AgammaX = 18.3%; Ggamma = 70.3%; Agamma = 11.4% STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A GAT->AAT mutation at codon 73; confirmed by gene mapping NOTES Found in Caucasian newborn babies; Hb FX 12.2% of total Hb REFERENCES 1. Chen, S-S., Webber, B.B., Wilson, J.B., and Huisman, T.H.J.: Biochim. Biophys. Acta, 832:242, 1985. Hb F-Yamaguchi Agamma80(EF4)Asp->Asn; 75(E19)Ile->Thr ELECTROPHORESIS Hb FX moves between Hb S and Hb C at alkaline pH IEF About the same CHROMATOGRAPHY Hb FX can be isolated by DEAE-cellulose chromatography CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting or reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported; presumed mutation GAT->AAT at codon 80 NOTES Found in Japanese newborn babies; quantity in the heterozygote 30-35%; its occurrence is associated with a Ggamma-thal REFERENCES 1. Fuyuno, K., Torigoe, T., Ohba, Y., Matsuoka, M., and Miyaji, T.: Hemoglobin, 5:139, 1981. 2. Nakatsuji, T., Ohba, Y., and Huisman, T.H.J.: Am. J. Hematol., 16:189, 1984. 3. Wada, Y., Fujita, T., Kidoguchi, K., and Hayashi, A.: Hum. Genet., 72:196, 1986. Hb F-Siena Agamma121(GH4)Glu->Lys; 75(E19)Ile->Thr ELECTROPHORESIS Hb FX moves slower than Hb A2 at alkaline pH IEF Not reported CHROMATOGRAPHY Not reported CHAIN SEPARATION Not reported STRUCTURE STUDIES Tryptic digestion of gammaX chain; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported; presumed mutation GAA->AAA at codon 121 NOTES Found in an Italian baby; quantity in the heterozygote ~20% of total Hb REFERENCES 1. Care, A., Marinucci, M., Massa, A., Maffi, D., Sposi, N.M., Improta, T., and Tentori, L.: Hemoglobin, 7:79, 1983. Hb F-Charlotte, Hb F-Sassari, Hb F-Waynesboro IDENTIFICATION These variants were discovered by reversed phase HPLC; no separation by electrophoretic or chromatographic procedures. The gammaX chain of each carrier eluted at the same position on a reversed phase column. The differences are the presence of an additional AgammaT variant in the babies with Hb F-Sassari and Hb F-Waynesboro. CHAIN SEPARATION Quantities of the chains: Ggamma gammaX Agamma AgammaT Hb F-Charlotte baby 72.5 9.7 17.8 0 Hb F-Sassari baby 37.1 32.4 19.3 11.2 Hb F-Waynesboro baby 43.0 29.2 14.4 13.3 DNA ANALYSES Extensive DNA sequencing analysis has shown the following: The three babies have a normal chromosome with a normal Ggamma gene and a normal Agamma gene. The Ggamma gene of the second chromosome of the Hb F-Charlotte baby is also normal, but that of the Hb F-Waynesboro baby is mutated at codon 75 (GgammaX with ATA->ACA or Ile->Thr). Thus, the total Ggamma level in the Hb F from the Hb F-Charlotte baby is normal at 72.5%, and that in the Hb F-Waynesboro baby is also normal [Ggamma (43.0%) + gammaX (29.2%) = 72.2%]. The sequences of the Agamma genes in both babies suggest a limited gene conversion by replacing a segment of the Agamma gene by that of a Ggamma gene, which makes the 3' end of the gene different from that of a normal Agamma gene. Both hybrid genes have an ATA->ACA mutation at codon 75 (Ile->Thr), while that in the Hb F-Charlotte baby has an additional GCA->GGA mutation at codon 136. The products of these hybrid genes will occupy different positions in the chromatogram. Hb F-Charlotte gammaX = AgammaX = Agamma (75 Ile->Thr; 136 Ala->Gly) Hb F-Waynesboro gammaX = GgammaX = Ggamma (75 Ile->Thr) REFERENCES 1. Plaseska, D., Kutlar, F., Wilson, J.B., Fei, Y.J., and Huisman, T.H.J.: Hemoglobin, 14:617, 1980. 2. Ferranti, P., Barone, F., Pucci, P., Malorni, A., Marino, G., Pilo, G., Manca, L., and Masala, B.: Hemoglobin, 18:307, 1994. 3. Gu, L-H., Oner, C., and Huisman, T.H.J.: Hemoglobin, 19:413, 1995. Hb Boyle Heights alpha6(A4)Asp->0 HEMATOLOGY Normal in the heterozygote ELECTROPHORESIS Hb X moves between Hb S and Hb F at alkaline pH, and with Hb A at acidic pH CHROMATOGRAPHY Hb X and Hb A separate on a DEAE-cellulose column STRUCTURE STUDIES Tryptic digestion of Hb X; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Not reported FUNCTION STUDIES Increased oxygen affinity STABILITY Unstable OCCURRENCE Found in members of a Mexican family OTHER INFORMATION Quantity in the heterozygote 14% REFERENCES 1. Johnson, C.S., Schroeder, W.A., Shelton, J.B., and Shelton, J.R.: Hemoglobin, 7:125, 1983. 2. Zhao, W., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 14:637, 1990. Hb Taybe alpha38(C3) or alpha39(C4) Thr->0 (alpha1) HEMATOLOGY Normal in the heterozygote; perhaps slight microcytosis ELECTROPHORESIS No resolution CHROMATOGRAPHY No resolution STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis DNA ANALYSES Sequence analysis has identified a frameshift (-ACC) at codon 38 or 39 of the alpha1 gene FUNCTION STUDIES Unknown STABILITY Unstable OCCURRENCE Found in a few Arabian families in Israel OTHER INFORMATION Quantity in the heterozygote not known; occurred in combination with a nondeletional alpha-thal; homozygosity has been described; this person suffered from severe hemolytic anemia REFERENCES 1. Girodon, E., M'Rad, A., Martin, J., Goossens, M., Galacteros, F., Rosa, J., Gisselbrecht, C., Boiron, M., Cohen, I.J., Jaber, L., Tamari, H., Goshen, J., Zaizov, R., and Wajcman, H.: Blood, 80:388a (Suppl. 1), 1992. 2. Galacteros, F., Girodon, E., M'Rad, A., Martin, J., Goossens, M., Jaber, L., Cohen, I.J., Tamary, H., Goshen, Y., Zaizov, R., and Wajcman, H.: C.R. Acad. Sci. Paris, 317:437, 1994. 3. Pobedimskaya, D.D., Molchanova, T.P., Streichman, S., and Huisman, T.H.J.: Am. J. Hematol., 47:198, 1994. Hb Natal alpha140(HC2)-alpha141(HC3) Tyr-Arg->0 HEMATOLOGY Modest erythrocytosis (PCV 0.55-0.56 l/l) ELECTROPHORESIS Hb X moves faster than Hb A at alkaline pH and in IEF CHROMATOGRAPHY Hb X elutes ahead of Hb A from a cation exchange HPLC column STRUCTURE STUDIES Tryptic digestion of alphaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; acid hydrolysis DNA ANALYSES A TAC->TAA mutation at codon 140 of the alpha2 gene FUNCTION STUDIES Increased oxygen affinity; no Bohr effect; no heme-heme interaction STABILITY Normal OCCURRENCE Found in an Asian Indian and his father OTHER INFORMATION None REFERENCES 1. Jogessar, V.B., Westermeyer, K., Webber, B.B., Wilson, J.B., Hu, H., Gonzalez-Redondo, J.M., Kutlar, A., and Huisman, T.H.J.: Biochim. Biophys. Acta, 951:36, 1988. Hb Leiden beta6(A3) or beta7(A4) Glu->0 HEMATOLOGY Mild hemolytic anemia; more severe when drug induced or by viral infection; reticulocytosis ELECTROPHORESIS Hb X moves in the position of Hb S at alkaline pH; no separation from Hb A at acidic pH CHROMATOGRAPHY Hb X elutes between Hb A2 and Hb A from an anion exchange column STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting or cation exchange chromatography; HPLC; amino acid analysis DNA ANALYSES Not reported FUNCTION STUDIES Slightly increased oxygen affinity; normal Bohr effect and cooperativity; decreased response to 2,3-DPG and IHP STABILITY Unstable OCCURRENCE Found in a few families from The Netherlands, China, USA, South Africa, Mexico, Yugoslavia OTHER INFORMATION Quantity in heterozygotes 19-31%; found in combination with betao-thal, causing severe hemolytic anemia REFERENCES 1. De Jong, W.W.W., Went, L.N., and Bernini, L.F.: Nature, 220:788, 1968. 2. Nagel, R.L., Rieder, R.F., Bookchin, R.M., and James, G.W.: Biochem. Biophys. Res. Commun., 53:1240, 1973. 4. Rieder, R.F. and James, G.W., III: J. Clin. Invest., 54:948, 1974. 3. Lie-Injo, L.E., Ganesan, J., Randhawa, Z.I., Peterson, D., and Kane, J.P.: Am. J. Hema-tol., 2:335, 1977. 4. Rieder, R.F. and James, G.W.: Blood, 47:489, 1976. 5. Zeng, Y-T., Huang, S-Z., Zhou, X-D., Chen, R-J., Yi, S-C., and Wang, C-J.; Chinese Med. J., 60:581, 1980. 6. Perlman, M.M., Wiltshire, B.G., Stevens, K., Cassel, R., and Lehmann, H.: S.A. Med. J., 59:537, 1981. 7. Juricic, D., Ruzdic, I., Beer, Z., Efremov, G.D., Casey, R., and Lehmann, H.: Hemoglobin, 7:271, 1983. Hb Lyon beta17(A14)-beta18(A15) Lys-Val->0 HEMATOLOGY Slight anemia in the heterozygote; Heinz bodies present after treatment with acetylphenylhydrazine ELECTROPHORESIS Hb X moves faster than Hb A in cellulose acetate electrophoresis at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by fingerprinting and cation exchange chromatography; amino acid analysis; final identification made with an automatic sequenator DNA ANALYSES Not done FUNCTION STUDIES Increased oxygen affinity STABILITY Slightly unstable OCCURRENCE Found in members of a French-Spanish-North African family living in France OTHER INFORMATION Quantity in the heterozygote 37% REFERENCES 1. Cohen-Solal, M., Blouquit, Y., Garel, M.C., Thillet, J., Gaillard, L., Creyssel, R., Gibaud, A., and Rosa, J.: Biochim. Biophys. Acta, 351:306, 1974. Hb Freiburg beta23(B5)Val->0 HEMATOLOGY Mild hemolytic anemia with cyanosis in the heterozygote ELECTROPHORESIS Hb X moves in the position of Hb F in starch gel electrophoresis at alkaline pH CHROMATOGRAPHY Hb X and Hb A separate in both cation and anion exchange HPLC STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis DNA ANALYSES Not done FUNCTION STUDIES Increased oxygen affinity; metHb with specific spectrum STABILITY Unstable OCCURRENCE Found in members of a German family OTHER INFORMATION Quantity in heterozygotes 27-32% REFERENCES 1. Betke, K. and Kleihauer, E.: Schweiz. Med. Wschr., 42:1316, 1962. 2. Jones, R.T., Brimhall, B., Huisman, T.H.J., Kleihauer, E., and Betke, K.: Science, 154:1024, 1966. Hb Higashitochigi (or HT) beta24(B6) or beta25(B7) Gly->0 HEMATOLOGY MetHb; cyanosis; normal hematology; reticulocytosis ELECTROPHORESIS Hb X focuses as a dark brown band behind Hb A and Hb F CHROMATOGRAPHY Hb X separates from Hb A on an anion exchange HPLC column (between Hb A and Hb A2); the betaX chain separates from betaA and alpha on a reversed phase HPLC column (elution order: betaA, alpha, betaX) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; sequencing DNA ANALYSES A deletion of three nts at codons 24-25 (GGTGGT->GGT) FUNCTION STUDIES MetHb formation STABILITY Unstable OCCURRENCE Found in a Japanese child, but not in the parents OTHER INFORMATION MetHb 16.5%; spectrum slightly abnormal; normal after addition of KCN REFERENCES 1. Fujisawa, K., Yamashiro, Y., Hattori, Y., Ohba, Y., Kajita, T., Kageyama, S., and Arita, J.: Hemoglobin, 17:467, 1993. Hb Bruxelles beta41(C7) or beta42(CD1) Phe->0 HEMATOLOGY Severe hemolytic anemia; splenomegaly; Heinz bodies; reticulocytosis ELECTROPHORESIS Hb X moves between Hb A and Hb F in IEF CHROMATOGRAPHY The betaX chain separates from betaA and alpha by reversed phase HPLC (elution order: betaX, betaA, alpha) STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by reversed phase HPLC; amino acid analysis; automated sequencing DNA ANALYSES Not reported FUNCTION STUDIES Decreased oxygen affinity of whole blood STABILITY Unstable OCCURRENCE Found in a Belgian child, but not in the parents OTHER INFORMATION Quantity in the heterozygote ~35% (chain analysis) REFERENCES 1. Blouquit, Y., Bardakdjian, J., Lena-Russo, D., Arous, N., Perrimond, H., Orsini, A., Rosa, J., and Galacteros, F.: Hemoglobin, 13:465, 1989. Hb Niteroi beta43(CD2)-beta45(CD4) Glu-Ser-Phe->0 OR beta42(CD1)-beta44(CD3) Phe-Glu-Ser->0 HEMATOLOGY Marked hemolytic anemia with reticulocytosis and Heinz bodies ELECTROPHORESIS Not reported CHROMATOGRAPHY Not reported STRUCTURE STUDIES Not reported DNA ANALYSES Not reported FUNCTION STUDIES MetHb formation STABILITY Unstable OCCURRENCE Found in a 26-year-old non-white Brazilian male, but not in his relatives OTHER INFORMATION Splenectomy eliminated the need for transfusions (no detailed description of this interesting abnormality was found in the literature) REFERENCES 1. Praxedes, H. and Lehmann, H.: Abstract 400, Proceedings of the 14th International Congress of Hematology, Sao Paulo, Brazil, 1972. Hb Tochigi beta56(D7)-beta59(E3) Gly-Asn-Pro-Lys->0 HEMATOLOGY Chronic hemolytic anemia ELECTROPHORESIS Hb X moves ahead of Hb A at alkaline pH; Hb X moves faster to the anode than Hb A at acidic pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES pCMB; tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not done FUNCTION STUDIES Not reported; metHb STABILITY Unstable OCCURRENCE Found in three members of a Japanese family OTHER INFORMATION Quantity in the heterozygote 20-25% REFERENCES 1. Shibata, S., Miyaji, T., Ueda, S., Matsuoka, M., Iuchi, I., Yamada, K., and Shinkai, N.: Proc. Jpn. Acad., 46:440, 1970. 2. Yamada, K., Shinkai, N., Nakazawa, S., Yamada, Z., Saito, K., Miwa, S., Miyaji, T., and Shibata, S.: Acta Haematol. Jap., 34:484, 1971. Hb Saint-Antoine beta74(E18)-beta75(E19) Gly-Leu->0 HEMATOLOGY Mild hemolytic anemia in the heterozygote ELECTROPHORESIS No separation obtained at alkaline pH CHROMATOGRAPHY Not reported STRUCTURE STUDIES pCMB; digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported FUNCTION STUDIES Normal or nearly normal STABILITY Slightly unstable OCCURRENCE Found in a 25-year-old female of Mediterranean origin OTHER INFORMATION None REFERENCES 1. Najman, A., Duhamel, G., Andre, R., Buc, H., Wajcman, H., Labie, D., and Schapira, G.: Nouv. Rev. Fr. d'Hematol., 13:803, 1973. 2. Wajcman, H., Labie, D., and Schapira, G.: Biochim. Biophys. Acta, 295:495, 1973. Hb Vicksburg beta75(E19)Leu->0 HEMATOLOGY Microcytosis and hypochromia in the heterozygote ELECTROPHORESIS No separation observed CHROMATOGRAPHY Hb X can be isolated on a DEAE-Sephadex column from the proband's lysate which contained Hb F and Hb A2 and no Hb A; Hb X moves like Hb A STRUCTURE STUDIES Tryptic digestion of betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported FUNCTION STUDIES Not reported STABILITY Normal OCCURRENCE Found in a 6-year-old Black male and presumably in his mother OTHER INFORMATION Quantity in the heterozygote not reported; found in association with beta+-thal REFERENCES 1. Adams, J.G., III, Steinberg, M.H., Newman, M.V., Morrison, W.T., Benz, E.J., Jr., and Iyer, R.: Proc. Natl. Acad. Sci. USA, 78:469, 1981. Hb Tours beta87(F3)Thr->0 HEMATOLOGY Mild hemolytic anemia in the heterozygote ELECTROPHORESIS Hb X moves like Hb S at alkaline pH CHROMATOGRAPHY Hb X was isolated on a cation exchange (Bio-Rex 70) column STRUCTURE STUDIES Tryptic digestion of AE-betaX chain; separation of peptides by cation exchange chromatography; amino acid analysis; sequencing DNA ANALYSES Not reported FUNCTION STUDIES Increased oxygen affinity; the unstable Hb readily loses heme STABILITY Unstable OCCURRENCE Found in a 40-year-old French male OTHER INFORMATION Quantity in the heterozygote about 25% REFERENCES 1. Najman, A., Duhamel, G., Andre, R., Buc, H., Wajcman, H., Labie, D., and Schapira, G.: Nouv. Rev. Fr. d'Hematol., 13:803, 1973. 2. Wajcman, H., Labie, D., and Schapira, G.: Biochim. Biophys. Acta, 295:495, 1973. Hb Gun Hill beta91(F7)-beta95(FG1) Leu-His-Cys-Asp-Lys->0 HEMATOLOGY Compensated hemolytic anemia with Heinz bodies after incubation with brilliant cresyl blue; reticulocytosis ELECTROPHORESIS Hb X1 (the larger component) migrates with Hb A2 at alkaline pH CHROMATOGRAPHY Hb X can be isolated on a DEAE-cellulose column; it elutes before Hb A STRUCTURE STUDIES Tryptic digestion; separation of peptides by fingerprinting; amino acid analysis DNA ANALYSES Not reported FUNCTION STUDIES Increased oxygen affinity; decreased cooperativity; no Bohr effect STABILITY Unstable; increased dissociation OCCURRENCE Found in members of a Caucasian family of German-English ancestry, and in a Black female living in Alabama OTHER INFORMATION Quantity in the heterozygote 22-26% REFERENCES 1. Bradley, T.B., Wohl, R.C., and Rieder, R.F.: Science, 157:1581, 1967. 2. Rieder, R.F. and Bradley, T.B.: Blood, 32:355, 1968. 3. Bradley, T.B., Parkhurst, L.J., Udem, L., and Gibson, Q.H.: Proceedings of the Inter-American Symposium on Hemoglobins, Caracas, page 168, 1969. 4. Rieder, R.F.: J. Clin. Invest., 50:388, 1971. 5. Murari, J., Smith, L.L., Wilson, J.B., Schneider, R.G., and Huisman, T.H.J.: Hemoglobin, 1:267, 1977. Hb Coventry beta141(H19)Leu->0 (probably incorrect: Suggested Leu->Hydroxyleu) HEMATOLOGY No hematological abnormalities ELECTROPHORESIS No separation of Hb X and Hb A CHROMATOGRAPHY No separation reported STRUCTURE STUDIES pCMB; tryptic digestion; separation of peptides by fingerprinting or HPLC; amino acid analysis; sequencing DNA ANALYSES Not reported FUNCTION STUDIES Increased oxygen affinity? STABILITY Unstable OCCURRENCE Found in several families and is widespread OTHER INFORMATION The Hb Coventry anomaly always occurs in association with another unstable Hb (Hb Sydney, Hb Atlanta); it is likely incorrectly identified as a deletion of leucine at beta141; more likely is oxidation to hydroxyleucine [see Hb Atlanta; beta75 (E19)Leu->Pro] REFERENCES 1. Casey, R., Kynoch, P.A.M., Lang, A., Lehmann, H., Nozari, G., and Shinton, N.K.: Br. J. Haematol., 38:195, 1978. 2. Nozari, G., Rahbar, S., and Lehmann, H.: FEBS Lett., 95:88, 1978. 3. Brennan, S.O., Williamson, D., Symmans, W.A., and Carrell, R.W.: Hemoglobin, 7:303, 1983.