HETEROZYGOUS BETA-THALASSEMIA - RELATIONSHIP BETWEEN THE HEMATOLOGICAL PHENOTYPE AND THE TYPE OF BETA-THALASSEMIA MUTATION

In this study we have correlated the severity of the hematological features to the type of the beta-thalassemia mutation [codon 39 (C --> T), IVS-I nt 110 (G --> A), IVS-I nt 1 (G --> A), IVS-I nt 6 (T --> C), IVS-II nt 745 (C --> G), -87 (C --> G) and beta-6 (-1bp)], in a group of beta-thalassemia heterozygotes of Italian descent in whom we excluded the presence of iron deficiency or deletion alpha-thalassemia. The beta-thalassemia mutation was defined by dot blot analysis on amplified DNA with allelic specific oligonucleotide probes. We found that a) heterozygotes for beta+ IVS-I nt 6 and beta+ -87 mutations produce larger and better hemoglobinized red blood cells, and b) heterozygotes for beta+IVS-I nt 6 and beta+IVS-I nt 110 mutations have a less marked increase of Hb A2 levels as compared to heterozygotes for the other mutations investigated. These findings indicate that milder beta-thalassemia mutations such as the beta+IVS-I nt 6 and beta+ -87, express also in the heterozygous state a milder phenotype as compared to beta-degrees-thalassemia or severe beta+ thalassemia (beta+ IVS-I, nt 110). The Hb A2 levels, on the other hand, were not related to the severity of the mutation because of less marked increase was found in a mild (beta+IVS-I nt 6) as well in a severe (beta+IVS-I nt 110) mutation. From the practical point of view these findings should be adequately considered in carrier screening and genetic counselling.