MUTATION		Codon 127 (C->T); CAG(Gln)->TAG(stop codon)
AMINO ACID REPLACEMENT		None
TYPE OF BETA-THAL		beta° (dominant, inclusion body, beta-thal trait)
MECHANISM		This nonsense mutation results in the synthesis of a shorter beta chain (126 amino acids long) which is likely rapidly removed by proteolysis
IDENTIFICATION		Amplification of the beta-globin gene; DNA sequencing; allele specific amplification
HEMATOLOGY IN HETEROZYGOTE(S)		The 18-year-old proband had a moderate anemia (Hb 9.0 g/dl) with MCV 77 fl and MCH 24 pg; Hb A2 4.2%; Hb F 4.0%; reticulocytes 8.0%; beta/alpha chain synthesis ratio 0.67; mother and sister, with the same mutation, are asymptomatic but have a hypochromic microcytic anemia
HEMATOLOGY IN HOMOZYGOTE(S)		None
OCCURRENCE		In an English family
HAPLOTYPE		Not reported
FOUND IN COMBINATION WITH ABNORMAL HB(S)		None
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)		None
OTHER INFORMATION		The text of the paper reporting the mutation lists a CAA->TAA change, but Fig. 1 of that paper, showing the direct sequence, indicates a CAG->TAG mutation, as expected

REFERENCES
1.		Hall, G.W., Franklin, I.M., Sura, T., and Thein, S.L.: Br. J. Haematol., 79:342, 1991.

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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.