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.
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.|