title: Retrospective study of the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Guthrie cards from a large cohort of neonatal screening for cystic fibrosis.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a cAMP-activated chloride channel, and in individuals with both alleles of the gene mutated, symptoms of CF disease are manifest. With more than 300 mutations so far described in the gene the profile of mutant alleles in a population is specific to its ethnic origin. For an analysis with an unbiased recruitment of the CF alleles in neonates of similar origin (Normandy, France), we have retrospectively analyzed the Guthrie cards of affected newborns, diagnosed by the immunoreactive trypsinogen (IRT) assay. Analysis of the 27 exons of the CFTR gene using a GC clamp denaturing gradient gel electrophoresis (DGGE) assay has enabled us to identify over 96% of the mutated alleles. Two of these were novel mutations. We would like to propose this strategy as an efficient method of retrospective molecular genetic diagnosis that can be performed wherever Guthrie cards can be obtained. Knowledge of rare alleles could be a prerequisite for CF therapy in the future.
authors.affiliation: Centre de Biogénétique, Centre Départemental de Transfusion Sanguine, Brest, France.
authors.forename: C
authors.initials: C
authors.lastname: Verlingue
authors.forename: B
authors.initials: B
authors.lastname: Mercier
authors.forename: I
authors.initials: I
authors.lastname: Lecoq
authors.forename: M P
authors.initials: MP
authors.lastname: Audrézet
authors.forename: D
authors.initials: D
authors.lastname: Laroche
authors.forename: G
authors.initials: G
authors.lastname: Travert
authors.forename: C
authors.initials: C
authors.lastname: Férec
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D015997:Neonatal Screening; D012189:Retrospective Studies
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA