MUTATION IVS-I (-1) or codon 30 (G->C); AG^GTTGGT->AC^GTTGGT
AMINO ACID REPLACEMENT Position 30 AGG->ACG (Arg->Thr; Hb Monroe)
MECHANISM The G->C change in the AG dinucleotide, which is required for normal splicing and is part of codon 30 (the first two nts of the AGG codon), will prevent splicing completely and no normal mRNA is formed
IDENTIFICATION Amplification of the beta-globin gene; DNA sequencing; dot-blot analysis with allele specific probes; ASO
HEMATOLOGY IN HETEROZYGOTE(S) Hb 11.3 g/dl; MCV 56 fl; MCH 18.5 pg; Hb A2 4.4%; Hb F 1.0%
HEMATOLOGY IN HOMOZYGOTE(S) Transfusion-dependent beta-thal major (Refs. 3,4,5)
OCCURRENCE In a Black family, a few Tunisian, Indian, and United Arab Emirate families
HAPLOTYPE [- - + + - + + + +]
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) The proband was a compound heterozygote: -29 (A->G)/IVS-I-1(-1) (G->C); Hb 8.6 g/dl; MCV 80 fl; MCH 25.6 pg; Hb A2 3.6%; Hb F 16.5%; patient was quite often transfused

TABLE A.   Transfusion Requirements of Patients Homozygous or Compound Heterozygous for Hb Monroe (from the United Arab Emirates; Ref. 6)

Sex-Age Other Chromosome Alpha Gene Status First Transfusion
(in months)
F-8 Homozygous alphaalpha/alphaalpha 30
F-9 -101, C->T alphaalpha/alphaalpha None
F-18 IVS-I-110, G->A alphaalpha/alphaalpha 30
F-4 IVS-I-110, G->A alphaalpha/alphaalpha 64
F-10 IVS-I-110, G->A -alpha(-3.7)/alphaalpha 46
F-12 Cd 22, -AAGTTGG alphaalpha/alphaalpha 12
M-11 Cd 22, -AAGTTGG alphaalpha/alphaalpha 6
F-11 IVS-I-5, G->C alphaalpha/alphaalpha 5
F-7 619 bp deletion -alpha(-3.7)/alphaalpha 17

OTHER INFORMATION Several attempts have been made to isolate Hb Monroe with questionable results; none should be present. The IVS-I (-1) G->C change for the homozygous patient described in Ref. 4 is linked to a C->G mutation at position -42 of the beta-globin gene promoter
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. Chibani, J., Vidaud, M., Duquesnoy, P., Bergé-Lefranc, J.L., Pirastu, M., Ellouze, F., Rosa, J., and Goossens, M.: Hum. Genet., 78:190, 1988.
3. Fattoum, S., Guemira, F., Öner, C, Öner R., Li, H-W., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 15:11, 1991.
4. Fedorov, A.N., Nasyrova, F.Yu., Smirnova, E.A., Bocharova, T.N., and Limborska, S.A.: Hemoglobin, 17:275, 1993.
5. Gupta, R.B., Tiwary, R.S., Pande, P.L., Kutlar, F., Öner C., Öner, R., and Huisman, T.H.J.: Hemoglobin, 15:441, 1991.
6. El-Kalla, S. and Mathews, A.R.: Hemoglobin, 21:237, 1997.

This material is from the book A Syllabus of Thalassemia Mutations (1997) by Titus H.J. Huisman, Marianne F.H. Carver, and Erol Baysal, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1997 by Titus H.J. Huisman. All rights reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, microfilming and recording, or by any information storage and retrieval systems, without permission in writing from the Author.