The Spectrum of δ-Thalassemia in the Western Sicily.

The detection of β-thalassemia carriers is based on the correct estimation of HbA2 values.The diagnosis of β-thalassemia carriers may be more complicated in presence of δ-thalassemia because the interaction between δ and β-globin gene defects modifies the HbA₂ values. For this reason, we studied the spectrum of δ-globin gene mutations present in the Sicilian population, characterized by its very high heterogeneity in β-thalassemia genotype and phenotype. The samples were selected by screening and routine prenatal diagnoses counseling for thalassemia. Among 7153 samples studied for β-thalassemia, 205 samples were selected for HbA₂ levels ranging from 0.5% to 2.0% and normal haematology parameters, suspected of being δ-thal carriers in the absence of α and β-thalassemia or hemoglobin variants, and for HbA₂ levels from 2.1% to 4.6% in subjects suspected of compound heterozygotes for δ and β-thalassemia and between 1.4% and 2.0% for δ and α-thalassemia. We have considered the value of 2% as the treshold between normal and d-carrier subjects. One-hundred-eighty-three samples showed to be positive for δ-globin gene mutations.Twelve mutations were detected and among these five were new δ-globin gene defects (HbA₂-Catania, HbA₂-Corleone, HbA₂-Ventimiglia; HbA₂-Montechiaro and HbA₂-Bagheria) determining δ-globin gene variants and seven were already described mutations. Among these six of them were point mutations (HbA₂-Mitsero, HbA₂-NYU,HbA₂-Yialousa, HbA₂-Coburg, HbA₂-Fitzroy) and one a 7.2 Kb deletion mutation known as the δ-Corfù type, HBD g.5946_1262del. As it was previously shown in Sicily for β-thalassemia, only three mutations account for 91% (HbA₂-Yialousa, HbA₂-NYU, IVS II-3′ A→G) of the overall δ-globin gene defects. HbA₂-Yialousa (g.82G→T) is the most common mutation found in Sicilian population (81%) while the other eleven mutations are less frequent between 0.5 to 5.5%. These findings suggest that in Sicily δ-thalassemia is very common (2.5%) and as it was described, previously, for the β-thalassemia mutations,this also is very heterogeneous (twelve mutations). This information is noteworthy considering the implication that the interaction between β and δ-thalassemia could determine in terms of HbA2 decrease in subjects heterozygotes for β-thalassemia.