title: The spectrum of beta-thalassaemia mutations in Sicily.
abstract: To characterize beta-thalassaemia genes among the Sicilian population we have previously determined the DNA haplotypes in the beta-globin gene cluster of 99 beta-thal chromosomes. We found seven haplotypes, although 95 of 99 beta-thal chromosomes contained framework 1 and framework 3 beta genes. We have now determined the mutation in all 99 of these beta-thal genes by the use of oligonucleotide hybridization. PCR-amplification and direct genomic sequencing, and direct restriction analysis. Our results indicate that (1) the beta (0)-39 mutation is most frequent (35%); (2) beta(0)-39, IVS-1 nt 110 and IVS-1 nt 6 mutations account for 90% of beta-thal genes: (3) the IVS-1 nt 6 mutation is more frequent in thalassaemia intermedia (77%) than in Cooley's disease (34%): (4) the association between haplotypes and specific mutations is imperfect, but mutation spread has occurred within haplotypes containing the same beta-gene framework: (5) the beta(0)-39 and the IVS-1 nt 6 mutations, with a mutation spread to two major haplotypes, may be older than the IVS-1 nt 110 mutation: (6) these data make possible first-trimester prenatal diagnosis in many families (85%) in Sicily using only three pairs of oligonucleotides. In addition, a new mutation, a frameshift at codon 76 due to loss of a C residue, was found in a single beta-thal chromosome.
authors.affiliation: Department of Hematology, V. Cervello Hospital, Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Di Marzo
authors.forename: C E
authors.initials: CE
authors.lastname: Dowling
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Maggio
authors.forename: H H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D002648:Child; D002675:Child, Preschool; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D009154:Mutation; D011296:Prenatal Diagnosis; D012802:Sicily; D013789:Thalassemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D005914:Globins