title: Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies.
abstract: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an epithelial anion channel. Since the identification of the disease in 1938 and up until 2012, CF patients have been treated exclusively with medications aimed at bettering their respiratory, digestive, inflammatory and infectious symptoms. The identification of the CFTR gene in 1989 gave hopes of rapidly finding a cure for the disease, for which over 1950 mutations have been identified. Since 2012, recent approaches have enabled the identification of small molecules targeting either the CFTR protein directly or its key processing steps, giving rise to novel promising therapeutic tools. This review presents the current CFTR mutation classifications according to their clinical consequences and to their effect on the structure and function of the CFTR channel. How these classifications are essential in the establishment of mutation-targeted therapeutic strategies is then discussed. The future of CFTR-targeted treatment lies in combinatory therapies that will enable CF patients to receive a customized treatment.
authors.affiliation: Université Paris-Est, UMR_S955, UPEC, F-94000 Créteil, France; Inserm, U955, Equipe 11, F-94000 Créteil, France; AP-HP, Hôpital H. Mondor - A. Chenevier, Département de Génétique, F-94000 Créteil, France. Electronic address: pascale.fanen@inserm.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Fanen
authors.affiliation: Inserm, U955, Equipe 11, F-94000 Créteil, France; McGill University, Faculty of Medicine, Department of Physiology, Montréal, QC, Canada.
authors.forename: Adeline
authors.initials: A
authors.lastname: Wohlhuter-Haddad
authors.affiliation: Université Paris-Est, UMR_S955, UPEC, F-94000 Créteil, France; Inserm, U955, Equipe 11, F-94000 Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hinzpeter
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CFTR; CFTR-RD; Mutation; Therapy; Variants of unknown significance