title: Nonsense codon mutations in the terminal exon of the beta-globin gene are not associated with a reduction in beta-mRNA accumulation: a mechanism for the phenotype of dominant beta-thalassemia.
abstract: We present in vivo evidence that there is no reduction in beta-mRNA accumulation in patients with nonsense codons in the terminal exon of the beta-globin gene. Using reverse transcriptase/polymerase chain reaction (RT-PCR), beta-globin cDNA was isolated from the reticulocytes of individuals heterozygous for nonsense codon mutations in exons II and III of the beta-globin gene. Clinically asymptomatic individuals heterozygous for mutations causing premature termination of translation in exon II [beta(0)39(C-T) and F/S71/72(+A)] were found to have almost no mutant beta-cDNA, whereas patients with nonsense codon mutations in exon III [beta 121(G-T) and beta 127(C-T)] with the clinical phenotype of thalassemia intermedia had comparable levels of mutant and normal beta-cDNA. Translation of the mutant beta-mRNA from patients with nonsense codon mutations in exon III would give rise to truncated beta-globin chains, which could explain the more severe phenotype seen in these individuals.
authors.affiliation: MRC Molecular Haematology Unit, John Radcliffe Hospital, Oxford, UK.
authors.forename: G W
authors.initials: GW
authors.lastname: Hall
authors.forename: S
authors.initials: S
authors.lastname: Thein
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D003062:Codon; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism*; D015183:Restriction Mapping; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D018076:DNA, Complementary; D012333:RNA, Messenger; D005914:Globins