title: Promoter mutations producing mild beta-thalassaemia in the Italian population.
abstract: In this study we have investigated the molecular basis for a mild form of beta-thalassaemia in three patients of Italian descent. In two, belonging to different families and affected by a mild and late-presenting form of thalassaemia major, direct sequencing of amplified DNA detected a C----T substitution at position -87 of the beta-globin gene in the compound heterozygous state either with codon 39 nonsense mutation or beta +IVSI, nt 110 mutation. The -87 (C----T) mutation has been previously described, in combination with the beta +IVSI, nt 110 mutation, in a single patient with thalassaemia intermedia. Both our patients showed a more severe phenotype as compared to that resulting from compound heterozygosity for a severe beta-thalassaemia mutation and another promoter mutation (-87, C----G) at the same position. In the third patient with the thalassaemia intermedia phenotype, we detected a novel promoter mutation, consisting in a C----A substitution at position -86, in combination with the codon 39 nonsense mutation. The results of this study indicate that different nucleotide substitutions affecting the proximal CACCC box of the beta-globin gene in combination with severe beta-thalassaemia, produce a mild form of thalassaemia ranging in severity from thalassaemia intermedia to late-presenting thalassaemia major.
authors.affiliation: Istituto di Ricerca sulle Talassemie e Anemie Mediterranee CNR, Cagliari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Meloni
authors.forename: M C
authors.initials: MC
authors.lastname: Rosatelli
authors.forename: V
authors.initials: V
authors.lastname: Faà
authors.forename: R
authors.initials: R
authors.lastname: Sardu
authors.forename: L
authors.initials: L
authors.lastname: Saba
authors.forename: S
authors.initials: S
authors.lastname: Murru
authors.forename: G V
authors.initials: GV
authors.lastname: Sciarratta
authors.forename: M
authors.initials: M
authors.lastname: Baldi
authors.forename: N
authors.initials: N
authors.lastname: Tannoia
authors.forename: A
authors.initials: A
authors.lastname: Vitucci
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013789:Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; D004247:DNA