Genetic heterogeneity of beta-thalassemia in southeast Sicily

In this study we have defined the spectrum of the beta-thalassemia mutations, the beta-thalassemia haplotypes, and the genotype-to-phenotype correlations in a large number of patients with different beta-thalassemia conditions. Seventeen different beta-thalassemia mutations were detected which included one chromosome each with Hb Dhonburi and Hb Lepore. Five alleles, namely, codon 39 (C-->T), IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-II-745 (C-->G), and IVS-I-1 (G-->A), account for 90% of all beta-thalassemia mutations in 846 thalassemic chromosomes studied. Haplotyping for a large number of subjects showed that the five common mutations are linked to a few haplotypes. The presence of milder mutations, mainly IVS-I-6 (T C), in about 19% of our patients explains some of the clinical variables. Among the 37 patients with thalassemia of intermediate severity, only 6 were homozygous or compound heterozygous for two severe alleles. The type of beta-thalassemia is the main factor responsible for differences in the phenotypic expression of the disease in patients with Hb S-beta-thalassemia; patients with Hb S-beta(+)-thalassemia are less severely affected than those with Hb S-beta(0)-thalassemia. The five most frequent mutations have comparable distributions all over Sicily.