title: The p.Gly622Asp (G622D) mutation, frequently found in Reunion Island and in black populations, is associated with a wide spectrum of CF and CFTR-RD phenotypes.
abstract: Examination of genotype-phenotype correlations along with functional evaluation of CFTR mutations may not be straightforward. The c.1865G>A, p.Gly622Asp (G622D), located at the NBD1 C terminus of the CFTR protein, was initially reported in patients with male infertility. However, the substitution of Gly622 by an aspartic acid in vitro would perturb the local structure or even affect the CFTR folding itself. In order to determine whether p.Gly622Asp affects the risk of developing a CFTR-Related disorder (CFTR-RD) or cystic fibrosis (CF), we analyzed the phenotype of subjects bearing the p.Gly622Asp mutation. We report molecular and clinical analyses in eleven unrelated patients with CF or CFTR-RD with compound heterozygosity for the p.Gly622Asp mutation. On the basis of the clinical features presented by the eleven patients, we postulate that the p.Gly622Asp might be associated with a wide spectrum of phenotypes including classical cystic fibrosis.
authors.affiliation: AP-HP, Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France.
authors.forename: Heller
authors.initials: H
authors.lastname: Marion
authors.affiliation: AP-HP, Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France.
authors.forename: Gaitch
authors.initials: G
authors.lastname: Natacha
authors.affiliation: AP-HP, Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France.
authors.forename: Martinez
authors.initials: M
authors.lastname: Brigitte
authors.affiliation: Service de Génétique, Centre Hospitalier Saint Denis, Saint Denis, La Réunion, France.
authors.forename: Cartault
authors.initials: C
authors.lastname: François
authors.affiliation: Service de Génétique, Centre Hospitalier Saint Denis, Saint Denis, La Réunion, France.
authors.forename: Renouil
authors.initials: R
authors.lastname: Michel
authors.affiliation: Laboratoire de Génétique Moléculaire, IURC, Institut Universitaire de Recherche Clinique, 34093 Montpellier Cedex 5, France.
authors.forename: Theze
authors.initials: T
authors.lastname: Corinne
authors.affiliation: AP-HP, Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France.
authors.forename: Girodon
authors.initials: G
authors.lastname: Emmanuelle
authors.affiliation: AP-HP, Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France; Université Paris Descartes Paris, Institut Cochin, INSERM U1016, Paris, France. Electronic address: thierry.bienvenu@inserm.fr.
authors.forename: Bienvenu
authors.initials: B
authors.lastname: Thierry
mesh_terms: D000293:Adolescent; D044383:Black People; D002648:Child; D003550:Cystic Fibrosis / Q000208:ethnology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D017508:Reunion / Q000453:epidemiology
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA