An initiation codon mutation as a cause of beta-thalassemia in a Belgian family.
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 [- + - + + + +].
Wildmann
C
C
Department of Clinical Biology, University of Louvain, Brussels, Belgium.
Larondelle
Y
Y
Vaerman
J L
JL
Eeckels
R
R
Martiat
P
P
Philippe
M
M
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*
D003062:Codon; D005914:Globins