TYPE Indian Ggamma(Agammadeltabeta)°-Thal (inversion); (see Fig. 16)
CAUSE This abnormality is caused by a major rearrangement, including an inversion of the entire sequence between the Agamma and beta genes, and two deletions of the flanking DNA sequences. The inversion occurs between the 3' Agamma gene and beta-IVS-II. The 3' end deletion is located between the 3' end of the beta gene and exon 3 of the beta gene, while the 5' end deletion removes 75% of the Agamma gene, leaving the 5' side of the gene intact. The two deletions total 8.5 kb of DNA and the inversion involves a 15.5 kb fragment. The sequence of the inverted DNA segment is retained.
DETECTION Gene mapping with various enzymes and probes. The summary of deletion breakpoints and that of the inversion is as follows: the breakpoint of the smaller 5' side deletion occurs between the PstI/ XbaI and 0.6 kb EcoRI sites, near the 3' end of the Agamma gene. The inversion breakpoints are between the 0.6 kb EcoRI site and between the HindIII/EcoRI sites in the 3' Agamma gene. The deletion in the downstream region extends from a region between the HindIII/EcoRI sites to exon 3 of the beta gene. For more detailed information on the restriction mapping, readers are invited to consult the references below.
PHENOTYPE Homozygotes have a thalassemia intermedia-like phenotype. Moderate anemia, jaundice, hepatosplenomegaly, and marked thalassemic RBC morphology are typical. The Hb F level is 100% with Ggamma chains only. No Hb A2 is detectable in homozygotes. A typical hematology is: Hb 9.9 g/dl; RBC 4.9 x 1012/l; MCV 71 fl; MCH 20 pg; alpha/gamma ratio 5.1. Heterozygotes show microcytosis, hypochromia, and typical beta-thal trait-like hematology: Hb 11.2-12.5 g/dl; MCV 77-78 fl; MCH 23-25 pg; Hb A2 2.0-2.4%; Hb F 9.7-12.3%; alpha/gamma+beta ratio 1.2-2.2.
DISTRIBUTION This major rearrangement was found in several unrelated families from India, Bangladesh, and Kuwait. In one Asian Indian family this deltabeta-thal occurs together with the high oxygen affinity variant Hb Headington or beta72(E16)Ser->Arg (Ref. 4).
1. Amin, A.B., Pandya, N.L., Diwin, P.P., Darbre, P.D., Kattamis, C., Metaxotou-Mavromati, A., White, J.M., Wood, W.G., Clegg, J.B., and Weatherall, D.J.: Br. J. Haematol., 43:537, 1979.
2. Jones, R.W., Old, J.M., Trent, R.J., Clegg, J.B., and Weatherall, D.J.: Nature, 291:39, 1981.
3. Trent, R.J., Jones, R.W., Clegg, J.B., Weatherall, D.J., Davidson, R., and Wood, W.G.: Br. J. Haematol., 57:279, 1984.
4. Rochette, J., Barnetson, R., Kiger, L., Kister, J., Littlewood, T.J., Webster, R., Poyart, C., and Thein, S.L.: Br. J. Haematol., 86:118, 1994.

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.