A new mutation, 3905insT, accounts for 4.8% of 1173 CF chromosomes in Switzerland and causes a severe phenotype.
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.
Hergersberg
M
M
Institut für Medizinische Genetik, Universität Zürich, Switzerland. hergie@medgen.unizh.ch
Balakrishnan
J
J
Bettecken
T
T
Chevalier-Porst
F
F
Brägger
C
C
Burger
R
R
Einschenk
I
I
Liechti-Gallati
S
S
Morris
M
M
Schorderet
D
D
Thonney
F
F
Moser
H
H
Malik
N
N
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
C505032:CFTR protein, human; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator