title: A new mutation, 3905insT, accounts for 4.8% of 1173 CF chromosomes in Switzerland and causes a severe phenotype.
abstract: We have analysed 1173 cystic fibrosis (CF) chromosomes from Switzerland for eight mutations in the CF transmembrane conductance regulator (CFTR) gene. This permitted the identification of 88.5% of all mutations present. A novel insertion mutation in exon 20 of the CFTR gene, 3905insT, was discovered. This mutation accounted for 4.8% of CFTR gene mutations in Switzerland and has since been identified in other populations of probable Swiss descent. It is associated with a highly variable clinical phenotype but always with pancreatic insufficiency. Haplotype analysis with three intragenic microsatellites in the CFTR gene showed that the mutation is associated with a haplotype rarely identified on other CFTR alleles and, therefore, that the frequency of the mutation in Switzerland is explained by a founder effect of a relatively recent mutation event.
authors.affiliation: Institut für Medizinische Genetik, Universität Zürich, Switzerland. hergie@medgen.unizh.ch
authors.forename: M
authors.initials: M
authors.lastname: Hergersberg
authors.forename: J
authors.initials: J
authors.lastname: Balakrishnan
authors.forename: T
authors.initials: T
authors.lastname: Bettecken
authors.forename: F
authors.initials: F
authors.lastname: Chevalier-Porst
authors.forename: C
authors.initials: C
authors.lastname: Brägger
authors.forename: R
authors.initials: R
authors.lastname: Burger
authors.forename: I
authors.initials: I
authors.lastname: Einschenk
authors.forename: S
authors.initials: S
authors.lastname: Liechti-Gallati
authors.forename: M
authors.initials: M
authors.lastname: Morris
authors.forename: D
authors.initials: D
authors.lastname: Schorderet
authors.forename: F
authors.initials: F
authors.lastname: Thonney
authors.forename: H
authors.initials: H
authors.lastname: Moser
authors.forename: N
authors.initials: N
authors.lastname: Malik
mesh_terms: D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D017931:DNA Primers; D018703:Founder Effect; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013557:Switzerland / Q000453:epidemiology
chemical_list: C505032:CFTR protein, human; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator