Molecular pathogenesis and clinical variability of β‐thalassemia syndromes among Indians

Sixty-four homozygous b-thalassemia patients comprising 40 patients with b-thalassemia major and 24 patients with b-thalassemia intermedia were investigated for the nature of their b-thalassemia mutations, associated a-thalassemia, and XmnI polymorphism in the gamma gene which are known to affect the clinical course of the disease. This study was undertaken to look for the contribution of these associated factors in reducing the clinical severity of homozygous b-thalassemia from a severe disease to a b-thalassemia intermedia phenotype. Clinical severity of these patients 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 different b-thalassemia mutations were encountered among 128 b-thalassemia chromosomes. It was observed that the nature of the b-thalassemia mutations was not very different between the b-thalassemia major and b-thalassemia intermedia groups in our patients, but co-inheritance of one or more a-globin gene deletions (˛a 3.7 ) and the presence of the XmnI polymorphism were associated with lesser severity of the disease in Indians. Am. J. Hematol. 68:75‐80, 2001. © 2001 Wiley-Liss, Inc.