MUTATION | -202 (C->G) Ggamma; nd-HPFH | ||
---|---|---|---|
IDENTIFICATION | Cloning; DNA sequencing | ||
HEMATOLOGY IN HETEROZYGOTE(S) | Normal; Hb F 16.7 (14.0-21.0)% (n=5) Ggamma nearly 100% (determined with the chemical gamma-CB3 procedure); Hb A2 1.75 (1.3-2.2)% (n=5) | ||
HEMATOLOGY IN HOMOZYGOTE(S) | Not observed | ||
OCCURRENCE | In a few Black families | ||
HAPLOTYPE | Not determined | ||
FOUND IN COMBINATION WITH ABNORMAL HB(S) | With Hb S: normal hematology; Hb F 20.1 (18.0-23.5)% (n=4); Hb A2 2.3 (2.1-2.6)% (n=4); Hb A 30.0 (24.0-36)% (n=4) | ||
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) | Not observed | ||
MECHANISM | This mutation in a binding site of the ubiquitous proteins SpI and GTi increases the Sp-I binding which may cause an overexpression of the Ggamma-globin gene; another possibility: destabilization of an intramolecular triplex present in this section of the 5' flanking region |
REFERENCES | |||
1. | Collins, F.S., Stoeckert, C.J., Jr., Serjeant, G.R., Forget, B.G., and Weissman, S.M.: Proc. Natl. Acad. Sci. USA, 81:4894, 1984. | ||
2. | Huisman, T.H.J., Miller, A., and Schroeder, W.A.: Am. J. Hum. Genet., 27:765, 1975. |