title: Heterozygous beta-thalassemia: relationship between the hematological phenotype and the type of beta-thalassemia mutation.
abstract: In this study we have correlated the severity of the hematological features to the type of the beta-thalassemia mutation [codon 39 (C----T), IVS-I nt 110 (G----A), IVS-I nt 1 (G----A), IVS-I nt 6 (T----C), IVS-II nt 745 (C----G), -87 (C----G) and beta 6 (-1 bp)], in a group of beta-thalassemia heterozygotes of Italian descent in whom we excluded the presence of iron deficiency or deletion alpha-thalassemia. The beta-thalassemia mutation was defined by dot blot analysis on amplified DNA with allelic specific oligonucleotide probes. We found that a) heterozygotes for beta+ IVS-I nt 6 and beta+ -87 mutations produce larger and better hemoglobinized red blood cells, and b) heterozygotes for beta+ IVS-I nt 6 and beta+ IVS-I nt 110 mutations have a less marked increase of Hb A2 levels as compared to heterozygotes for the other mutations investigated. These findings indicate that milder beta-thalassemia mutations such as the beta+ IVS-I nt 6 and beta+ -87, express also in the heterozygous state a milder phenotype as compared to beta o-thalassemia or severe beta+ thalassemia (beta+ IVS-I, nt 110). The Hb A2 levels, on the other hand, were not related to the severity of the mutation because of less marked increase was found in a mild (beta+ IVS-I nt 6) as well in a severe (beta+ IVS-I nt 110) mutation. From the practical point of view these findings should be adequately considered in carrier screening and genetic counselling.
authors.affiliation: Istituto di Clinica e Biologia dell'Età Evolutiva, Università Studi Cagliari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rosatelli
authors.forename: G B
authors.initials: GB
authors.lastname: Leoni
authors.forename: T
authors.initials: T
authors.lastname: Tuveri
authors.forename: M T
authors.initials: MT
authors.lastname: Scalas
authors.forename: A
authors.initials: A
authors.lastname: Mosca
authors.forename: R
authors.initials: R
authors.lastname: Galanello
authors.forename: D
authors.initials: D
authors.lastname: Gasperini
authors.forename: A
authors.initials: A
authors.lastname: Cao
mesh_terms: D000328:Adult; D000483:Alleles; D004247:DNA / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics; D006443:Hemoglobin A2 / Q000032:analysis / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015345:Oligonucleotide Probes; D010641:Phenotype; D013789:Thalassemia / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*
chemical_list: D015345:Oligonucleotide Probes; D004247:DNA; D006443:Hemoglobin A2