MUTATION IVS-I-5 (G->C)
 
AMINO ACID REPLACEMENT None
TYPE OF BETA-THAL beta+ (severe)
MECHANISM The G->C mutation at nt 5 of the IVS-I greatly reduces the efficiency of splicing of the normal 5' splicing site (see scheme) 
Codon #          30   IVS-I             
Normal           AG^  GTTGGTATCAAGGTTACA
IVS-I-5 (G->C)   AG^  GTTGCTATCAAGGTTACA
IDENTIFICATION Amplification or cloning of the beta-globin gene; DNA sequencing; dot-blot analysis of amplified DNA with allele specific probes; ARMS
HEMATOLOGY IN HETEROZYGOTE(S) Hb 10-12 g/dl; MCV 65-70 fl; MCH 18-22 pg; Hb A2 5.0-5.5%
HEMATOLOGY IN HOMOZYGOTE(S) Severe thalassemia major; 5-8% Hb A in the untransfused patients
OCCURRENCE Frequent in Asian Indian, UAE, and East Asian populations (see Tables III, V, IX, X, XI, and XII)
HAPLOTYPE VII [+ O - - - - - - +]
FOUND IN COMBINATION WITH ABNORMAL HB(S) Hb Dhonburi (Ref. 4); Hb D; Hb S (n=17): Hb 8.2 g/dl; MCV 72.2 fl; MCH 22.1 pg; Hb A2 4.7%; Hb F 14.7%; Hb A estimated at 3-5% (from Ref. 3);Hb E-beta+-thal (n=6): Hb 7.0 g/dl; MCV 65 fl; MCH 21.8 pg; Hb A2 (as delta) 5.6%; Hb F 36.0%; Hb A 6.4% (unpublished data)
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) Numerous different alleles
OTHER INFORMATION None
       
REFERENCES
1. Treisman, R., Orkin, S.H., and Maniatis, T.: Nature, 302:591, 1983.
2. Kazazian, H.H., Jr., Orkin, S.H., Antonarakis, S.E., Sexton, J.P., Boehm, C.D., Goff, S.C., and Waber, P.G.: EMBO J., 3:593, 1984.
3. Kulozik, A.E., Bail, S., Kar, B.C., Serjeant, B.E., and Serjeant, G.R.: Br. J. Haematol., 77:215, 1991.
4. Divoky, V., Bissé, 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.

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.