Beta-thalassaemia in Cubans: novel allele increases the genetic diversity at the HBB locus in the Caribbean.

In order to establish the molecular basis of beta-thalassaemia in Cubans, a total of 75 unrelated individuals, with beta-thalassaemia major (7), Hb S-beta-thalassaemia (28), Hb C-beta-thalassaemia (1), and beta-thalassaemia trait (39) yielding 82 beta-thalassaemia alleles, were analyzed. Seventeen different point mutations were identified accounting for 93% of the beta-thalassaemia alleles studied, revealing a high genetic heterogeneity at the HBB locus in this population. The more prevalent mutations, namely, CD 39 (C --> T) (30.5%), -29 (A --> G) (13.4%), IVS-I-110 (G --> A) (8.5%), and IVS-II-1 (G --> A) (8.5%), reflect the Mediterranean and African predominant ancestry of the extant Cuban population. We also report the identification of a novel allele, IVS-I-108 (T --> C), that possibly activates a cryptic branch site, in a beta-thalassaemia carrier with no other molecular defect within the beta-globin gene and its proximal promoter. This study shows that prenatal diagnosis of beta-thalassaemia should be feasible in about 60% of at-risk pregnancies by direct detection of selected point mutations. However, due to the wide spectrum of mutations, and in order to offer fully informative prenatal diagnosis to more than 87% of at-risk couples, the screening for beta-thalassaemia mutations in Cubans should be performed by using a general point mutation detection method, such as DGGE (denaturing gradient gel electrophoresis).