Codon.24.(T-@A),.GGT(Gly)-@GGA(Gly).html


MUTATION		Codon 24 (T->A); GGT(Gly)->GGA(Gly)

AMINO ACID REPLACEMENT		None
TYPE OF BETA-THAL		beta⁺
MECHANISM		This T->A change activates a 5' splicing site at codons 24, 25, and 26: GGT·GGT·GAG->GGA·G^GT·GAG
IDENTIFICATION		Cloning of the beta-globin gene; sequencing; amplification and sequencing of amplified DNA; dot-blot analysis with allele specific probes; ASO
HEMATOLOGY IN HETEROZYGOTE(S)		Hb 10.9-12.5 g/dl; MCV 70-73 fl; MCH 21.5-23.0 pg; Hb A₂ 4.75-5.05%; Hb F 0.6-3.3%
HEMATOLOGY IN HOMOZYGOTE(S)		None observed
OCCURRENCE		In American Blacks; Japanese
HAPLOTYPE		II [- O- + + - + + +]
FOUND IN COMBINATION WITH ABNORMAL HB(S)		None reported
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)		Found in combination with -29 (A->G) causing a thalassemia intermedia (Hb 9-13 g/dl; MCV 60-70 fl; MCH 18-25 pg; Hb A₂ 3.1-9.3%; Hb F 24.2-66.5%
OTHER INFORMATION		The activation of this splice site leads to ~75% reduction in the accumulation of normal mRNA


REFERENCES
1.		Goldsmith, M.E., Humphries, R.K., Ley, T., Cline, A., Kantor, J.A., and Nienhuis, A.W.: Proc. Natl. Acad. Sci. USA, 80:2318, 1983.
2.		Hattori, Y., Yamane, A., Yamashiro, Y., Matsuno, Y., Yamamoto, Ki., Yamamoto, Ku., Ohba, Y., and Miyaji, T.: Hemoglobin, 13:657, 1989.
3.		Gonzalez-Redondo, J.M., Stoming, T.A., Lanclos, K.D., Gu, Y.C., Kutlar, A., Kutlar, F., Nakatsuji, T., Deng, B., Han, I.S., McKie, V.C., and Huisman, T.H.J.: Blood, 72:1007, 1988.

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.