MUTATION TAA->CAA at codon 142 of the alpha2 gene
AMINO ACID REPLACEMENT Stop codon->Gln +30 additional amino acids (Hb Constant Spring)
TYPE OF ALPHA-THAL alpha-Thal-2 [alpha(T)alpha/alphaalpha]
MECHANISM This T->C mutation results in an extension of the alpha chain with 31 amino acid residues; a stop codon is found at the new codon 173
IDENTIFICATION Originally by protein analysis; in later times by amplification of the alpha2-globin gene and DNA sequencing; dot-blot analysis with allele specific probes; ASO
HEMATOLOGY IN HETEROZYGOTE(S) Hb 10.0-13.5 g/dl; MCV 61-87 fl; MCH 17-27 pg; Hb A2 2.4-3.1%
HEMATOLOGY IN HOMOZYGOTE(S) Hb 11-12 g/dl; MCV 73-75 fl; MCH 21-24 pg; Hb A2 1.8-2.0%
OCCURRENCE Rather widespread in East Asian populations; mainly Chinese; incidence in Bangkok 1.5%
HAPLOTYPE Not determined
FOUND IN COMBINATION With different alpha-thal alleles:
- -(SEA)/alpha(CS)alpha= Hb H disease;
-alpha(3.7)/alpha(CS)alpha= alpha-thal-1 type of condition;
-alpha(4.2)/alpha(CS)alpha= same
OTHER INFORMATION Hb CS is present for >2% in the heterozygote and >5% in homozygotes; the protein is unstable
1. Milner, P.F., Clegg, J.B., and Weatherall, D.J.: The Lancet, i:729, 1971.
2. Clegg, J.B., Weatherall, D.J., and Milner, P.F.: Nature, 234:337, 1971.
3. Efremov, G.D., Wrightstone, R.N., Huisman, T.H.J., Schroeder, W.A., Hyman, C., Ortega, J., and Williams, K.: J. Clin. Invest., 50:1628, 1971.
4. Lie-Injo, L.E., Ganesan, J., Clegg, J.B., and Weatherall, D.J.: Blood, 43:251, 1974.
5. Thonglairoam, V., Winichagoon, P., Fucharoen, S., Tanphaichitr, V.C., Pung-amritt, P., Embury, S.H., and Wasi, P.: Am. J. Hematol., 38:277, 1991.
6. Xu, X-M., Zhang, J-Z., and Li, S-K.: Hemoglobin, 18:61, 1994.

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.