Molecular characterization of β-thalassemia mutations in Guadeloupe

In order to perform genetic counselling and prenatal diagnosis of Hb-S-β-thalassemia disease and β-thalassemia, we have delineated the spectrum of β-thalassemia alleles in the Guadeloupean population. A sample of 63 unrelated families was analyzed including 70 β-thalassemia carriers, 52 Hb-S-β-thalassemia, and 8 patients with different β-thalassemic hemoglobinopathies. Among the eleven mutations identified, four of them [-29 (A → G), IVS-1-5 (G → A), IVS-II-1 (G → A), and IVS-I-5 (G → C)] account for 77.6% of the β-thalassemia chromosomes present in the studied families. The seven other variants, CD 24 (T → A), IVS-I-2 (T → C), Poly A (T → C), -88 (C → T), IVS-II-849 (A → G), Hb E, and Hb Lepore are less frequent. As a result, Hb S-β ⁺-thalassemia type 1 (low Hb A values: 5-15% together with Hb S-β(o)-thalassemia phenotypes are as frequent as Hb S-β ⁺-thalassemia type 2 (high Hb A values: 20-30%) in the Guadeloupean population. Patients with Hb S-β ⁺-thalassemia type 2 have milder hematological manifestations of the disease compared to patients with Hb S-β(o)-thalassemia and Hb S-β ⁺-thalassemia type 1. This first report on the type and nature of β-thalassemia mutations in Guadeloupe shows that prenatal diagnosis of Hb S-β-thalassemia and β-thalassemia should be feasible by direct detection of point mutation in most cases.