RESUMO
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-thalassemia carriers, 52 Hb-S-beta-thalassemia, and 8 patients with different beta-thalassemic hemoglobinopathies. Among the eleven mutations identified, 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-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- 11-849 (A --> G), Hb E, and Hb Lepore are less frequent. As a result, Hb S-beta+-thalassemia type 1 (low Hb A values: 5-15%) together with Hb S-beta(omicron)-thalassemia phenotypes are as frequent as Hb S-beta+-thalassemia type 2 (high Hb A values: 20-30%) in the Guadeloupean population. Patients with Hb S-beta+-thalassemia type 2 have milder hematological manifestations of the disease compared to patients with Hb S-beta(omicron)-thalassemia and Hb S-beta+-thalassemia type 1. This first report on the type and nature of beta-thalassemia mutations in Guadeloupe shows that prenatal diagnosis of Hb S-beta-thalassemia and beta-thalassemia should be feasible by direct detection of point mutation in most cases.
Assuntos
Globinas/genética , Talassemia beta/genética , África Ocidental/etnologia , Alelos , Anemia Falciforme/epidemiologia , Anemia Falciforme/etnologia , Anemia Falciforme/genética , Frequência do Gene , Aconselhamento Genético , Guadalupe/epidemiologia , Hemoglobina Falciforme/genética , Humanos , Índia/etnologia , Região do Mediterrâneo/etnologia , Traço Falciforme/complicações , Traço Falciforme/epidemiologia , Traço Falciforme/etnologia , Traço Falciforme/genética , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/etnologiaRESUMO
In order to delineate the spectrum of á-thalassaemia (á-thal) mutations in the Guadeloupean population, we have analysed a representative sample of 59 unrelated families carrying a á-thalassaemia trait. Using gene amplification, hybridization with 32P-labelled oligonucleotide probes and sequencing of amplified DNA, 8 different á-thal mutations were identified in 62 members of 36 families. Four of these families carried a á§-thal trait whereas, in the 32 others, a á+-thal trait has been identified. All patients were á-thal heterozygous: 30 had Hb S/á-thal, 1 had Hb C/á-thal, 1 had HPFH/á-thal whereas the remaining 30 had a Hb A/á-thal genotype. Four of the á-thal mutations detected [-29 (A -> G), IVS-I-5 (G -> C), IVS-II-1 (G -> A) and CD 24 (T -> A)] accounted for approximately 88.8 percent of the á-thalassaemia chromosomes identified. The four other variants, -88 (C -> T), IVS-I-5 (G -> A), IVS-I-5 (G -> T) and IVS-I-2 (T -> C), are less frequent. The á-thalassaemia mutations in 23 families remained unidentified and are under investigation. This study provides data for prenatal diagnosis of sickle-cell disease for Hb S/á-thalassaemia genotypes (AU)