V-a.   The GGammaAGamma(DeltaBeta)°-Thalassemias

(Deltabeta)°-thalassemia is relatively common in the populations of the Mediterranean area where the so-called Sicilian type is found. In addition, nine other types have been detected in other parts of the world. In all instances, the deletion involves (part of) the delta- globin gene and the beta-globin gene. The sizes of the deletions are shown in Fig. 14; for several types the 3' end of the deletion is found in the L1 repeat 3' to the beta-globin gene.

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FIG. 14. The sizes and locations of 10 deletions resulting in a (deltabeta)°-thalassemia.

Heterozygous individuals generally have a mild anemia (Hb 10-12 g/dl) with a distinct microcytosis and hypochromia (MCV 60-65 fl; MCH 18-24 pg). The level of Hb A2 is (low) normal (1.8-2.9%) which is the result of an increased activity of the delta-globin gene in trans. Hb F is elevated (5-15%) with Ggamma values which are mainly determined by the presence or absence of the C->T mutation at position -158 (Ggamma). Homozygotes produce no Hb A and no Hb A2 but Hb F only. Their clinical course is one of thalassemia intermedia with a Hb level of 8-10 g/dl. Interactions of (deltabeta)°-thal with beta-thal determinants and with Hb S have been reported. A beta°/(deltabeta)°-thal compound heterozygote usually has severe disease resembling beta-thalassemia major; exact diagnosis often requires family studies. A Hb S/ (deltabeta)°-thal compound heterozygote is less severely affected, perhaps because high levels of Hb F (20-35%) are present in such individuals. Identification of known (deltabeta)°-thal alleles is greatly facilitated with the use of PCR and appropriate primers, and the identification of abnormal fragments which include the deletion (1).

1. Craig, J.E., Barnetson, R.A., Prior, J., Raven, J.L., and Thein, S.L.: Blood, 83:1673, 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.