TYPE Macedonian (deltabeta)°-Thal (see Fig. 14)
 
CAUSE This condition is characterized by an 11.5 kb deletion including the delta and beta genes. A smaller deletion further 3' to the beta gene removes another 1.6 kb of DNA. An inversion of 7.6 kb that includes the entire L1 repetitive sequences occurs between the larger 5' and the smaller 3' deletions. The shorter L1 repeat further downstream remains intact.
DETECTION Extensive restriction mapping with numerous enzymes and hybridizations to a gamma probe and the pRK 29 probe localized the 5' and 3' end breakpoints, respectively. The DNA sequences at the breakpoints were elucidated by cloning and sequencing. The complex rearrangement resulting in the deletion of two DNA segments divided by an inverted DNA segment included an 11,646 bp deletion of the delta and beta genes (5' end deletion) and a 1,592 bp deletion located between the two 3' L1 repeats 5' to the pRK 29 probe. The two deletions are separated by a 7,645 bp inverted DNA segment spanning the entire L1 repeat sequence.
PHENOTYPE The deletion was originally found in a Macedonian individual and has also been discovered in a 25-year-old Turkish patient who was diagnosed with homozygous (deltabeta)°-thal. She had massive hepatosplenomegaly, and was only slightly microcytic and hypochromic: Hb 12.1 g/dl; MCV 73 fl; MCH 24 pg; Hb analysis showed Hb F only. Both parents, siblings, and the patient's first son were asymptomatic, and had the same abnormality. The heterozygous relatives showed microcytosis and hypochromia: MCV 60-76 fl; MCH 19-25 pg; Hb 12.5-14.1 g/dl; normal Hb A2 levels (2.2-2.6%), and increased Hb F (6.7-12.8%).
DISTRIBUTION Found in a Macedonian patient and a Turkish patient from Antalya.
       
REFERENCES
1. Efremov, G.D., Nikolov, N., Bakioglu, I., and Huisman, T.H.J.: Blood, 68:971, 1986.
2. Kulozik, A.E., Bellan-Koch, A., Kohne, E., and Kleihauer, E.: Blood, 79:2455, 1992.
3. Craig, J.E., Efremov, G.D., Fisher, C., and Thein, S.L.: Blood, 85:1146, 1995.

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.