title: Genetic heterogeneity of beta-thalassemia in southeast Sicily.
abstract: 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.
authors.affiliation: Division of Pediatric Hematology and Oncology, University of Catania, Sicily, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Schilirò
authors.forename: F
authors.initials: F
authors.lastname: Di Gregorio
authors.forename: P
authors.initials: P
authors.lastname: Samperi
authors.forename: E
authors.initials: E
authors.lastname: Mirabile
authors.forename: R
authors.initials: R
authors.lastname: Liang
authors.forename: M A
authors.initials: MA
authors.lastname: Cürük
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: 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*
chemical_list: D006451:Hemoglobin, Sickle; D006455:Hemoglobins, Abnormal; C065670:hemoglobin Dhonburi; D005319:Fetal Hemoglobin; C037659:hemoglobin Lepore