Codon.28.(T-@G),.CTG(Leu)-@CGG(Arg).html


MUTATION		Codon 28 (T->G); CTG(Leu)->CGG(Arg)

AMINO ACID REPLACEMENT		Leu->Arg (Hb Chesterfield)
TYPE OF BETA-THAL		beta⁺ (inclusion body or dominant beta-thal)
MECHANISM		The T->G change results in the introduction of an arginine at position 28 which makes the Hb molecule very unstable resulting in a clinical phenotype of a rather severe beta-thal
IDENTIFICATION		Amplification of the beta-globin gene; sequencing
HEMATOLOGY IN HETEROZYGOTE(S)		Transfusion-dependent from age 10; splenectomized at age 13; Hb 7-9 g/dl; MCV 86.6 fl; MCH 30.3 pg; reticulocytes 10%; Hb A₂ 4%; Hb F 3.4%; erythroblastosis; inclusion bodies
HEMATOLOGY IN HOMOZYGOTE(S)		Not observed
OCCURRENCE		In a 34-year-old English female
HAPLOTYPE		Incompletely studied
FOUND IN COMBINATION WITH ABNORMAL HB(S)		Not observed
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)		Not observed
OTHER INFORMATION		Hb Chesterfield is severely unstable; not detected by electrophoretic methods; radiolabeled beta^X elutes behind beta^A on a CMC column; both parents are normal; six siblings also appear normal; likely a de novo mutation


REFERENCES
1.		Thein, S.L., Best, S., Sharpe, J., Paul, B., Clark, D.J., and Brown, M.J.: Blood, 77:2791, 1991.

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.