VI-e.   Alpha-Thalassemia-1 Determinants With Intact Alpha-Globin Genes But With the Deletion of the Locus Control Region HS-40

During the past several years five different deletions have been described, each usually in one single family, which caused an alpha-thal-1 phenotype but is characterized by deletions located 5' to the psizeta1-globin gene, while both alpha-globin genes are intact. These deletions have in common the deletion of an erythroid-specific DNase I hypersensitive site, called HS-40, which is located about 40 kb 5' to the zeta2-globin gene. This HS-40 sequence is critical to the expression of the alpha2-alpha1-globin gene cluster. In his recent review Higgs (1) summarized all five deletions; these are shown in Fig. 25 which is taken from that summary. It is worth noting that the deletion (alphaalpha)IdF was found in a patient with Hb H disease who carried the 3.7 kb deletion in trans.

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FIG. 25. Deletions upstream of the alpha-globin gene cluster that give rise to alpha-thal. The position of the upstream regulatory element (HS-40) is shown. The extent of the upstream deletions are illustrated as solid bars, with the regions of uncertainty for the breakpoints shown as open boxes. Additional types were recently reported (7).

1. Higgs, D.R.: in The Haemoglobinopathies, edited by D.R. Higgs and D.J. Weatherall, Bailliere's Clinical Haematology, Vol. 6, page 117, W.B. Saunders Company, London, 1993.
2. Hatton, C.S.R., Wilkie, A.O.M., Drysdale, H.C., Wood, W.G., Vickers, M.A., Sharpe, J., Ayyub, H., Pretorius, I.M., Buckle, V.J., and Higgs, D.R.: Blood, 76:221, 1990.
3. Wilkie, A.O.M., Lamb, J., Harris, P.C., Finney, R.D., and Higgs, D.R.: Nature, 346:868, 1990.
4. Liebhaber, S.A., Griese, E-U., Weiss, I., Cash, F.E., Ayyub, H., Higgs, D.R., and Horst, J.: Proc. Natl. Acad. Sci. USA, 81:9431, 1990.
5. Ramao, L., Osorio-Almeida, L., Higgs, D.R., Lavinha, J., and Liebhaber, S.A.: Blood, 78:1589, 1991.
6. Ramao, L., Cash, F., Weiss, I., Liebhaber, S., Pirastu, M., Galanello, R., Loi, A., Paglietti, E., Ioannou, P., and Cao, A.: Hum. Genet., 89:323, 1992.
7. Higgs, D.R.: Report at the Thalassaemia and Haemoglobinopathies Meeting at Malta, April 1997.

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.