title: Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
abstract: Five different mutations have been identified in the gene causing cystic fibrosis (CF) through sequencing regions encompassing exons 1-8, including the 5' untranslated leader. Two of these apparent mutations are missense mutations, one in exon 3 (Gly to Glu at position 85; G85E) and another in exon 5 (Gly to Arg at 178; G178R), both causing significant changes in the corresponding amino acids in the encoded protein--cystic fibrosis transmembrane conductance regulator (CFTR). Two others affect the highly conserved RNA splice junction flanking the 3' end of exons 4 and 5 (621 + 1G----T, 711 + 1G----T), resulting in a probable splicing defect. The last mutation is a single-basepair deletion in exon 4, causing a frameshift. These five mutations account for the 9 of 31 non-delta F508 CF chromosomes in our Canadian CF family collection and they are not found in any of the normal chromosomes. Three of the mutations, 621 + 1G----T, 711 + 1G----T, and G85E, are found in the French-Canadian population, with 621 + 1G----T being the most abundant (5/7). There are two other sequence variations in the CFTR gene; one of them (129G----C) is located 4 nucleotides upstream of the proposed translation initiation codon and, although present only on CF chromosomes, it is not clear whether it is a disease-causing mutation; the other (R75Q) is most likely a sequence variation within the coding region.
authors.affiliation: Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Zielenski
authors.forename: D
authors.initials: D
authors.lastname: Bozon
authors.forename: B
authors.initials: B
authors.lastname: Kerem
authors.forename: D
authors.initials: D
authors.lastname: Markiewicz
authors.forename: P
authors.initials: P
authors.lastname: Durie
authors.forename: J M
authors.initials: JM
authors.lastname: Rommens
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA; D004252:DNA Mutational Analysis; D005091:Exons; D016368:Frameshift Mutation; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012326:RNA Splicing
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA