-29.(A-@G).html

MUTATION

-29 (A->G)

 -30  -25 
  |    |  
CATAAAAG->
CATGAAAG

AMINO ACID REPLACEMENT

None

TYPE OF BETA-THAL

beta⁺

MECHANISM

Decreased beta-globin gene transcription because of a reduced binding of transcription factors

IDENTIFICATION

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

HEMATOLOGY IN HETEROZYGOTE(S)

Hb 10-12 g/dl; MCV 68-73 fl; MCH 21.5-23.0 pg; Hb A₂ 4.95± 0.3% (n=64); Hb F 0.5-4.0%

HEMATOLOGY IN HOMOZYGOTE(S)

Hb 8.6-10.5 g/dl; RBC 3.95-5.85 x 10¹²/l; MCV 55-69 fl; MCH 17.5-22.0 pg; Hb F 25-67%; Hb A₂ 4.2-10.0%

OCCURRENCE

The most common mutation in Blacks; see Tables XIII and XV; in Chinese

HAPLOTYPE

[- + + - + + + + +] and [- - - - - + + + +]

FOUND IN COMBINATION WITH ABNORMAL HB(S)

	Hb	MCV	MCH	Hb A₂	Hb F	Hb A
with Hb S (n=42)	10.8	66.0	22.8	6.0	11.0	20.1
with Hb C (n=10)	10.2	59.5	20.0	5.8	6.3	18.9
with Hb O-Arab	12.2	71.0	21.5	6.6	10.4	19.4
with Hb N-Baltimore	12.0	90.0	27.0	5.4	4.7	16.3

FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)

With some other beta-thal alleles common among Blacks

OTHER INFORMATION

The higher than expected delta chain synthesis is due to the delta gene in cis to the beta-thal mutation; this -29 promoter mutation decreases the binding of transcriptional factors and indirectly increases binding to the delta promoter and transcription of the delta-globin gene


REFERENCES
1.		Antonarakis, S.E., Orkin, S.H., Cheng, T-C., Scott, A.F., Sexton, J.F., Trusko, S.P., Charache, S., and Kazazian, H.H., Jr.: Proc. Natl. Acad. Sci. USA, 81:1154, 1984.
2.		Atweh, G.F. and Forget, B.G.: Am. J. Hematol., 24:31, 1987.
3.		Huang, S., Wong, C., Antonarakis, S.E., Ro-Lien, T., Lo, W.H.Y., and Kazazian, H.H., Jr.: Hum. Genet., 74:162, 1986.
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.		Gonzalez-Redondo, J.M., Kutlar, F., Kutlar, A., Stoming, T.A., de Pablos, J.M^a., Kilinç, Y., and Huisman, T.H.J.: Br. J. Haematol., 70:85, 1988.
6.		Codrington, J.F., Li, H-W., Kutlar, F., Gu, L-H., Ramachandran, M., and Huisman, T.H.J.: Blood, 76: 1246, 1990.
7.		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.