Molecular pathogenesis and clinical variability of beta-thalassemia syndromes among Indians

Sixty-four homozygous beta -thalassemia patients comprising 40 patients wit h beta -thalassemia major and 24 patients with beta -thalassemia intermedia were investigated for the nature of their beta -thalassemia mutations, ass ociated alpha -thalassemia, and XmnI polymorphism in the gamma gene which a re known to affect the clinical course of the disease. This study was under taken to look for the contribution of these associated factors in reducing the clinical severity of homozygous beta -thalassemia from a severe disease to a beta -thalassemia intermedia phenotype. Clinical severity of these pa tients was assessed by the degree of transfusion dependency and the age at which the patient presented with symptoms. Globin chain synthetic ratio was taken as the biochemical pointer of severity of the disease. Eleven differ ent beta -thalassemia mutations were encountered among 128 beta -thalassemi a chromosomes. It was observed that the nature of the beta -thalassemia mut ations was not very different between the beta -thalassemia major and beta -thalassemia intermedia groups in our patients, but co-Inheritance of one o r more alpha -globin gene deletions (-alpha (3.7)) and the presence of the XmnI polymorphism were associated with lesser severity of the disease in In dians. Am. J. Hematol. 68:75-80, 2001. (C) 2001 Wiley-Liss, Inc.