Hb Bristol beta67(E11)Val->Asp
         
NOTE: A recent study by Rees et al (Ref. 3) concerns the analysis of the Hb Bristol abnormality in the original family and in two Japanese heterozygotes. All three have a GTG->ATG mutation by sequencing analysis as in Hb Alesha (beta67, Val->Met). Posttranslational modifications are believed to change some of the properties of the abnormal Hb such as an increased mobility; this could contribute to an an inaccurate identification. The formation of a Hb fraction in the Hb Alesha heterozygote with an Asp->Met replacement has not been reported
CONTACT Heme contact
HEMATOLOGY Congenital non-spherocytic hemolytic anemia with Heinz body formation; reticulocytosis
ELECTROPHORESIS Moves with Hb A at alkaline pH; no other reports available
CHROMATOGRAPHY Not reported
STRUCTURE STUDIES pCMB; tryptic digestion; separation of peptides by fingerprinting; amino acid analysis; sequencing
DNA ANALYSES Not reported (see Other Information)
FUNCTION STUDIES Decreased oxygen affinity, cooperativity, and Bohr effect
STABILITY Unstable
OCCURRENCE Found in an English male and not his parents; Ref. 1 describes the first clinical data
OTHER INFORMATION Quantity in the heterozygote 36%. The normally occurring codon GTG cannot be mutated through a single base change to GAT (Asp) or GAC (Asp). There are two possibilities: a) The Hb is misdiagnosed and is in fact Hb M-Milwaukee-I (GTG->GAG; Val->Glu) or b) the original codon in this subject was GTT or GTC; the two can be mutated to GAT (Asp) or GAC (Asp); further study of this patient is recommended
       
REFERENCES
1. Cathie, I.A.B.: Great Ormond St. J., 2:43, 1952.
2. Steadman, J.H., Yates, A., and Huehns, E.R.: Br. J. Haematol., 18:435, 1970.
3. Rees, D.C., Rochette, J., Green, B., Schofield, C.J., Ohba, Y., and Clegg, J.B.: Blood, 88:6a (Suppl. 1), 1995.


This material is from the book A Syllabus of Human Hemoglobin Variants (1996) by Titus H.J. Huisman, Marianne F.H. Carver, and Georgi D. Efremov, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1996 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 written permission.