title: [Functional characterization of naturally occurring CFTR mutants: interest for cystic fibrosis].
abstract: Cystic fibrosis is caused by mutations in the CFTR gene (Cystic Fibrosis Transmembrane conductance Regulator) encodes a protein mainly functioning as a chloride channel that regulates chloride and sodium transport in secretory epithelial cells. The past several years with advances in DNA analysis have seen an increased knowledge of the mutational spectrum for cystic fibrosis. The functional characterization of some naturally occurring CFTR mutants led to classification of mutations according to the mechanisms by which they disrupt CFTR function. This article reports the strategies that are currently available to evaluate the deleterious consequences of naturally occurring CFTR mutants. A number of in silico tools and molecular approaches are presented. The accurate knowledge of CFTR mutations causing or non-causing disease present obvious interest in both clinical diagnosis and research fields. A better understanding of the molecular defects associated with various CFTR mutations will provide a basis for development of novel pharmacologic compounds intended to correct transcriptional abnormalities or improve protein processing/trafficking. This is illustrated by the functional characterization of the first sequence variation identified in the CFTR minimal promoter, which allowed to address in original way the important and poorly understood regulation of expression of the CFTR gene.
authors.affiliation: Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Montpellier. marie-catherine.romey@igh.cnrs.fr
authors.forename: M-C
authors.initials: MC
authors.lastname: Romey
mesh_terms: D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005817:Genetic Counseling; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator