Clinical and molecular heterogeneity of β thalassaemia intermedia in Sri Lanka

Abstract

A third of all patients attending thalassaemia centres in Sri Lanka have non-transfusion dependent thalassaemia (NTDT). The majority of these have Hb E β-thalassaemia. The genetic basis of non-E β-thalassaemia intermedia (TI) was studied in an attempt to correlate their genotype with the phenotype. Fifty unrelated TI patients were identified from the main thalassaemia centres, assessed clinically and categorized into ‘mild’, ‘moderate’ and ‘severe’ groups. DNA analyses were performed using standard techniques. Seventeen patients were homozygous or compound heterozygous for β mutations. Five of the homozygotes who carried two mild β alleles had mild disease. Nine inherited two severe β alleles with either one or two α gene deletions; despite the α deletions, they had severe disease. Thirty three patients were heterozygous for a β mutation: IVSI-5 G>C was the commonest. Twenty eight of the heterozygotes carried excess α genes and had a mild-moderate phenotype. The clinical outcomes of this TI population were mostly explained by the genotypes linked to the α and β gene cluster. However, in a minority, the existence of other causative genetic determinants remains to be defined.