title: Structure-function analysis of a double-mutant cystic fibrosis transmembrane conductance regulator protein occurring in disorders related to cystic fibrosis.
abstract: A number of disorders related to cystic fibrosis have been described since the cloning of the cystic fibrosis gene, including infertility due to the congenital bilateral absence of the vas deferens. We have identified, in several patients, complex cystic fibrosis transmembrane conductance regulator genotypes like double-mutant alleles. We have now analyzed the structure-function relationships of one of these mutants, R74W-D1270N cystic fibrosis transmembrane conductance regulator, expressed in HeLa cells, to evaluate the contribution of each mutation in the phenotype. We found that R74W cystic fibrosis transmembrane conductance regulator appears to be a polymorphism, while D1270N cystic fibrosis transmembrane conductance regulator could be responsible for the congenital bilateral absence of the vas deferens phenotype. The combination of the two produced a more severe effect on the chloride conductance pathway as well as on the phenotype.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U.468, Service de Biochimie et Génétique, Hôpital Henri Mondor, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Fanen
authors.forename: J
authors.initials: J
authors.lastname: Clain
authors.forename: R
authors.initials: R
authors.lastname: Labarthe
authors.forename: P
authors.initials: P
authors.lastname: Hulin
authors.forename: E
authors.initials: E
authors.lastname: Girodon
authors.forename: P
authors.initials: P
authors.lastname: Pagesy
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: A
authors.initials: A
authors.lastname: Edelman
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D008322:Mammals; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: C505032:CFTR protein, human; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017868:Cyclic AMP-Dependent Protein Kinases