-88.(C-@T).html

MUTATION

-88 (C->T)

  -90  -85 
   |    |  
CCACACCCT->
CCACATCCT

AMINO ACID REPLACEMENT

None

TYPE OF BETA-THAL

beta⁺

MECHANISM

This C->T mutation decreases transcription of the beta-globin gene because of decreased binding by transcriptional factors

IDENTIFICATION

Cloning and amplification of the beta-globin gene; DNA sequencing; dot-blot analysis with allele specific probes (ASO)

HEMATOLOGY IN HETEROZYGOTE(S)

Hb 11.5-12.5 g/dl; MCV 70-74 fl; MCH 23-25 pg; Hb A₂ 5.65±0.3 (n=32); Hb F 2-4%; mild microcytosis and hypochromia

HEMATOLOGY IN HOMOZYGOTE(S)

(n=3); Hb 9.8-12.3 g/dl; MCV 56-71 fl; MCH 18-22 pg; Hb A₂ 4.0-9.5%; Hb F 40-72%; Hb A remainder

OCCURRENCE

In Black populations; see Table XV

HAPLOTYPE

[+ - - - - + + - ]; [- + + - + + + - +]

FOUND IN COMBINATION WITH ABNORMAL HB(S)

	Hb	MCV	MCH	Hb A₂	Hb F	Hb A
With Hb S (n=14)	10.3	67.5	22.3	6.4	14.8	17.9
With Hb C (n=3)	10.3	55.0	19.9	6.5	15.9	17.2

FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)

With alleles common among Blacks

OTHER INFORMATION

Unusually high Hb A₂ values in both heterozygotes and homozygotes; this mutation alters the binding of transcriptional factors to the beta promoter, and indirectly promotes the transcription of the delta-globin gene


REFERENCES
1.		Orkin, S.H., Antonarakis, S.E., and Kazazian, H.H., Jr.: J. Biol. Chem., 259:8679, 1984.
2.		Wong, C., Antonarakis, S.E., Goff, S.C., Orkin, S.H., Boehm, C.D., and Kazazian, H.H., Jr.: Proc. Natl. Acad. Sci. USA, 83:6529, 1986.
3.		Beris, Ph., Kitundu, M.N., Baysal, E., Öner, C., Lanclos, K.D., Dimovski, A.J., Kutlar, F., and Huisman, T.H.J.: Am. J. Hematol., 41:97, 1992.
4.		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.
5.		Huisman, T.H.J.: Acta Haematol., in press, 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.