-198.(T-@C).Agamma,.the.British.nd-HPFH.html

MUTATION

-198 (T->C) ^Agamma; the British nd-HPFH

IDENTIFICATION

Cloning and DNA sequencing; restriction enzyme analysis

HEMATOLOGY IN HETEROZYGOTE(S)

Normal (Ref. 1)	Normal (Ref. 4)
Hb F 8.5 (3.9-13.0)% (n=10)	Hb F 3.8 (1.8-5.8)% (n=12)
^Ggamma 8.0%; ^Agamma 92.0% (gammaCB-3)	nearly 100% ^Agamma (rp-HPLC)
Hb A₂ 2.35 (2.0-2.7)% (n=10)	Hb A₂ 2.4 (1.9-2.7)% (n=5)

HEMATOLOGY IN HOMOZYGOTE(S)

Three adults:

Hb F 19.4; 19.6; 20.4%;
^Ggamma 8.0%;
^Agamma 92.0% (gammaCB-3);
Hb A₂ 1.7; 1.6; 1.6%

OCCURRENCE

In a British family and an Australian family

HAPLOTYPE

Haplotype I [+ - - - - + + +]

FOUND IN COMBINATION WITH ABNORMAL HB(S)

Not reported

FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)

With beta-thal (Hb A₂ 5.2%; Hb F 7.9%; nearly 100% ^Agamma by rp-HPLC)

MECHANISM

The mutation alters the affinity of a transacting factor [see also -202 (C->G) ^Ggamma]


REFERENCES
1.		Weatherall, D.J., Cartner, R., Clegg, J.B., Macrae, I.A., and Mackenzie, A.: Br. J. Haematol., 29:205, 1975.
2.		Tate, V.E., Wood, W.G., and Weatherall, D.J.: Blood, 68:1389, 1986.
3.		Donald, J.A., Lammi, A., and Trent, R.J.: Hum. Genet., 80:69, 1988.
4.		Harvey, M.P., Motum, P., Lindeman, R., and Trent, R.J.: Exp. Hematol., 20:320, 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.