Molecular analysis of β(o)-thalassemia intermedia in Sardinia

Abstract

In this study we have carried out α- and β-globin gene analysis and defined the β-globin gene polymorphisms in a group of patients with thalassemia intermedia of Sardinian descent. A group of patients (109) with thalassemia major of the same origin served as control. Characterization of the β-thalassemia mutation showed either a frameshift mutation at codon 6 or a codon 39 nonsense mutation. We found that homozygotes for the frameshift mutation at codon 6 or compound heterozygotes for this mutation and for the codon 39 nonsense mutation develop thalassemia intermedia more frequently than thalassemia major. The frameshift mutation at codon 6 was associated with haplotype IX that contains the C-T change at position -158 5' to the G(γ) globin gene implicated in high γ chain production and thus the mild phenotype. In patients' homozygotes for codon 39 nonsense mutation, those with thalassemia intermedia more frequently had the two-gene deletion form of α-thalassemia, or functional loss of the α2 gene as compared with those with thalassemia major. In a few siblings with thalassemia major and intermedia, the thalassemia intermedia syndrome correlated with the presence of the -α/-α genotype. No cause for the mild phenotype was detected in the majority of patients who had not inherited either haplotype IX or α-thalassemia.