title: Benign missense variations in the cystic fibrosis gene.
abstract: The common mutation causing cystic fibrosis is a deletion of phenylalanine 508 (delta F508), which occurs in a putative nucleotide-binding fold of the gene product. We report two additional mutations, substitution of cysteine for phenylalanine 508 (F508C) and substitution of valine for isoleucine 506 (I506V). Three compound heterozygous persons, two delta F508/F508C and one delta F508/I506V, had normal clinical and epithelial physiological studies indicating that the F508C and I506V mutations are benign. This opportunity to study the in vivo function of these mutations suggests that amino acid substitutions are more benign than changes in the length of this portion of the putative nucleotide-binding fold. These mutations must be taken into account when performing molecular diagnosis and carrier detection for cystic fibrosis.
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M R
authors.initials: MR
authors.lastname: Knowles
authors.forename: R C
authors.initials: RC
authors.lastname: Boucher
authors.forename: W E
authors.initials: WE
authors.lastname: O'Brien
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002712:Chlorides / Q000378:metabolism; D002872:Chromosome Deletion; D003550:Cystic Fibrosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013542:Sweat / Q000378:metabolism
chemical_list: D002712:Chlorides