MUTATION		Codon 123 (-A); ACC(Thr)->-CC
AMINO ACID REPLACEMENT		An elongated betaX chain (Hb Makabe)
TYPE OF BETA-THAL		Dominant inclusion body beta-thal trait
MECHANISM		The deletion of A causes a frameshift and the synthesis of an elongated beta chain (156 amino acids) because of a new stop codon at codon 157 (TAA); this beta chain is highly unstable and is removed by proteolysis
IDENTIFICATION		Cloning of the beta-globin gene; sequencing of DNA; the frameshift eliminates an HphI site which can be used for identification
HEMATOLOGY IN HETEROZYGOTE(S)		The carrier was splenectomized at the age of 28 years: Hb 9.1 g/dl; MCV 101 fl; MCH 33.1 pg; 152 nRBC/100 WBC; Hb A2 3.7%; Hb F 12.9%; anisocytosis; poikilocytosis; inclusion bodies after incubation; beta/alpha ratio 0.55
HEMATOLOGY IN HOMOZYGOTE(S)		Not observed
OCCURRENCE		In a Japanese family; a 48-year-old and his brother and mother (both deceased)
HAPLOTYPE		[+ - - - - - - +]
FOUND IN COMBINATION WITH ABNORMAL HB(S)		None
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)		None
OTHER INFORMATION		The betaX variant could not be detected by electrophoresis, chromatography, or by stability tests

REFERENCES
1.		Fucharoen, S., Kobayashi, Y., Fucharoen, G., Ohba, Y., Miyazono, K., Fukumaki, Y., and Takaku, F.: Br. J. Haematol., 75:393, 1990.

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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.