title: An initiation codon mutation as a cause of beta-thalassemia in a Belgian family.
abstract: Nine asymptomatic members of a family of Belgian origin, spanning three generations, present typical features of heterozygous beta-thalassemia. Since no mutation was detected with a large panel of oligonucleotide probes, the thalassemia gene was investigated by direct sequencing of DNA segments amplified by the polymerase chain reaction. A T-->C transition was detected in the translation initiation codon (ATG). The mutation, which abolishes an Nco I restriction site, was further confirmed by enzymatic digestion as well as by dot-blot hybridization of the amplified products with allele-specific oligonucleotide probes. It produced a beta zero-thalassemia phenotype characterized by marked microcytosis and hypochromia, as well as by an in vitro beta/alpha chain synthesis ratio close to O.5. Search for haplotype linkage showed the mutation to be associated with haplotype IX [- + - + + + +].
authors.affiliation: Department of Clinical Biology, University of Louvain, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Wildmann
authors.forename: Y
authors.initials: Y
authors.lastname: Larondelle
authors.forename: J L
authors.initials: JL
authors.lastname: Vaerman
authors.forename: R
authors.initials: R
authors.lastname: Eeckels
authors.forename: P
authors.initials: P
authors.lastname: Martiat
authors.forename: M
authors.initials: M
authors.lastname: Philippe
mesh_terms: D001483:Base Sequence; D001530:Belgium; D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D005914:Globins