Molecular characterization of β-thalassemia intermedia: a report from Iran

Thalassemia intermedia is a clinical definition applied to patients whose clinical phenotype is milder than thalassemia major. To characterize different common mechanisms involving in pathogenesis of moderate to severe beta-thalassemia intermedia, we have studied four factors in 38 Iranian patients with thalassemia intermedia: beta-globin gene mutation, deletion in alpha-globin genes, presence of XmnI polymprphism and RFLP haplotype at beta-globin gene cluster. The results showed that 84.4% of patients were associated with severe mutations in beta-globin gene, mainly IVSII-1(G to A) (56.4%). The positive XmnI polymorphism was seen in 76.9% of the studied alleles which showed strong linkage to beta A degrees mutations and high level of fetal hemoglobin. Co-existence of alpha-globin gene deletions, beta(+) mutation and the most frequent of RFLP haplotype (-/-, +/+, -/+, +/+, +/+, +/+, -/-) were seen in 7.7, 12.8 and 17.9%, respectively. In this group of our study it seems the main ameliorating factor in the patients was co-inheritance of a positive XmnI polymorphism with beta A degrees mutation especially IVSII-1, which were associated with increased production of fetal hemoglobin. However, the other probable genetic factors should be investigated to describe genotype-phenotype correlation in thalassemia intermedia patients.