Molecular pathogenesis and clinical variability of homozygous beta0-thalassemia in populations of Jammu region of J&K state (India).

This study was undertaken to evaluate the variation in the clinical presentation of homozygous beta0-thalassemia from severe disease to a beta-thalassemia intermedia phenotype and to look for the contribution of associated factors in this variation of clinical course. Type of beta0-thalassemia mutations, associated alpha-thalassemia, and XmnI polymorphism in the gamma globin gene, which are known to affect the clinical course of the disease, were investigated from 15 homozygous beta0-thalassemia patients comprising 11 patients with beta-thalassemia major and 4 patients with beta-thalassemia intermedia. Transfusion dependency and the age at which the patient presented with symptoms were used to assess the degree of clinical severity of these patients. Three different beta0-thalassemia mutations viz. CD 41-42 (-TTCT), CD 8-9 (+G) and 619 bp deletion, were encountered among the 30 beta-thalassemia alleles. It was observed that the type of beta0-thalassemia mutations was not different between the two groups, but co-inheritance of one or more alpha-gene deletions and the presence of the XmnI polymorphism were associated with lesser severity of the disease.