TYPE HPFH-3; Indian (see Fig. 13)
 
CAUSE The deletion removes 48.5 kb of DNA starting from the 5' end of the psibeta gene to a region 30 kb downstream of the beta gene. Cloning and sequencing of the deletion junction and its comparison to HPFH-1 and HPFH-2 shows that the deletion is the result of a non-homologous recombinational event. The 5' breakpoint occurs in the Alu I family repeat 3' to the Agamma gene. The 3' breakpoint is located within a region that contains the following: a portion of an L1 repeat, a perfect 160 bp palindrome, and a set of 41 bp direct repeats that are translocated from another part of the human genome.
DETECTION Gene mapping and sequencing.
PHENOTYPE A significant difference in the Ggamma:Agamma ratio occurs between the Indian HPFH-3 and the other types of HPFH. The Ggamma:Agamma ratio averaged 65:35 in seven cases studied, while the total quantity of gamma chains produced in heterozygotes appeared to be the same in all three types. The average hematological values for the seven Indian HPHF-3 heterozygotes are: MCV 90.1±1.9 fl; Hb F 22.6±1.0%; Ggamma 69.3± 3.5%.
DISTRIBUTION Found in a few families from India.
       
REFERENCES
1. Schroeder, W.A., Huisman, T.H.J., and Sukumaran, P.K.: Br. J. Haematol., 25:131, 1973.
2. Kutlar, A., Gardiner, M.B., Headlee, M.G., Reese, A.L., Cleek, M.P., Nagle, S., Sukumaran, P.K., and Huisman, T.H.J.: Biochem. Genet., 22:21, 1984.
3. Henthorn, P.S., Mager, D.K., Huisman, T.H.J., and Smithies, O.: Proc. Natl. Acad. Sci. USA, 83:5194, 1986.

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.