MOLECULAR CHARACTERIZATION OF BETA-THALASSEMIA MUTATIONS IN GUADELOUPE

In order to perform genetic counselling and prenatal diagnosis of Hb-S -beta-thalassemia disease and beta-thalassemia, we have delineated the spectrum of beta-thalassemia alleles in the Guadeloupean population. A sample of 63 unrelated families was analyzed including 70 beta-thala ssemia carriers, 52 Hb-S-beta-thalassemia, and 8 patients with differe nt beta-thalassemic hemoglobinopathies. Among the eleven mutations ide ntified, four of them [-29 (A --> G), IVS-I-5 (G --> A), IVS-II-1 (G - -> A), and IVS-I-5 (G --> C)] account for 77.6% of the beta-thalassemi a chromosomes present in the studied families. The seven other variant s, 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 r esult, Hb S-beta(+)-thalassemia type 1 (low Hb A values: 5-15%) togeth er with Hb S-Po-thalassemia phenotypes are as frequent as Hb S-beta(+) -thalassemia type 2 (high Hb A values: 20-30%) in the Guadeloupean pop ulation. Patients with Hb S-beta(+)-thalassemia type 2 have milder hem atological manifestations of the disease compared to patients with Hb S-beta(0)-thalassemia and Hb S-beta(+)-thalassemia type 1. This first report on the type and nature of beta-thalassemia mutations in Guadelo upe shows that prenatal diagnosis of Hb S-beta-thalassemia and beta-th alassemia should be feasible by direct detection of point mutation in most cases. (C) 1996 Wiley-Liss, Inc.