MUTATION		Codon 109 (-G); GTG(Val)->-TG
AMINO ACID REPLACEMENT		Hb Manhattan
TYPE OF BETA-THAL		beta°
MECHANISM		This frameshift leads to the formation of an elongated beta chain of 156 amino acids because of a stop codon at codon 157 (TAA); this betaX chain was not recovered to any great extent and is rapidly catabolized
IDENTIFICATION		Amplification of the beta-globin gene; DNA sequencing
HEMATOLOGY IN HETEROZYGOTE(S)		Chronic hemolytic anemia; splenomegaly: Hb 8.5 g/dl; MCV 67 fl; MCH 22 pg; Hb A2 4.5%; reticulocytes 1.2%; no Heinz bodies; no inclusion bodies after incubation with methyl violet; beta/alpha ratio 0.5
HEMATOLOGY IN HOMOZYGOTE(S)		Not observed
OCCURRENCE		In a 78-year-old Lithuanian Ashkenazi female; the anemia was detected at the age of 23 years
HAPLOTYPE		Not reported
FOUND IN COMBINATION WITH ABNORMAL HB(S)		None
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)		None
OTHER INFORMATION		No abnormal peptides, representing the betaX chain, were observed after (short) incubations of red cells with 3H-leucine or 3H-tyrosine using reversed phase HPLC as separation procedure

REFERENCES
1.		Kazazian, H.H., Jr., Dowling, C.E., Hurwitz, R.L., Coleman, M., Stopeck, A., and Adams, J.G., III: Blood, 79:3014, 1992.

---

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.