Genetic heterogeneity of beta-thalassemia in southeast Sicily.
In this study we have defined the spectrum of the beta-thalassemia mutations, the beta-thalassemia haplotypes, and the genotype-to-phenotype correlations in a large number of patients with different beta-thalassemia conditions. Seventeen different beta-thalassemia mutations were detected which included one chromosome each with Hb Dhonburi and Hb Lepore. Five alleles, namely, codon 39 (C-->T), IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-II-745 (C-->G), and IVS-I-1 (G-->A), account for 90% of all beta-thalassemia mutations in 846 thalassemic chromosomes studied. Haplotyping for a large number of subjects showed that the five common mutations are linked to a few haplotypes. The presence of milder mutations, mainly IVS-I-6 (T C), in about 19% of our patients explains some of the clinical variables. Among the 37 patients with thalassemia of intermediate severity, only 6 were homozygous or compound heterozygous for two severe alleles. The type of beta-thalassemia is the main factor responsible for differences in the phenotypic expression of the disease in patients with Hb S-beta-thalassemia; patients with Hb S-beta(+)-thalassemia are less severely affected than those with Hb S-beta(0)-thalassemia. The five most frequent mutations have comparable distributions all over Sicily.
Schilirò
G
G
Division of Pediatric Hematology and Oncology, University of Catania, Sicily, Italy.
Di Gregorio
F
F
Samperi
P
P
Mirabile
E
E
Liang
R
R
Cürük
M A
MA
Ye
Z
Z
Huisman
T H
TH
D005319:Fetal Hemoglobin / Q000032:analysis; D008040:Genetic Linkage; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000032:analysis; D006455:Hemoglobins, Abnormal / Q000032:analysis*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012802:Sicily; D017086:beta-Thalassemia / Q000235:genetics*
D006451:Hemoglobin, Sickle; D006455:Hemoglobins, Abnormal; C065670:hemoglobin Dhonburi; D005319:Fetal Hemoglobin; C037659:hemoglobin Lepore