title: Cystic fibrosis in a low-incidence population: two major mutations in Finland.
abstract: The incidence of cystic fibrosis (CF) in Finland, 1:25,000 newborn, is one of the lowest in Caucasian populations. The delta F508 mutation accounts for 18/40 (45%) of CF chromosomes in Finland. Other mutations were therefore sought among the remaining 55%. Twelve out of 40 chromosomes (30%) were found to carry 394delTT, whereas G542X and 3732delA were each detected in one chromosome. Eight mutations remained unidentified using a testing panel for 26 mutations. Mutation 394delTT was associated exclusively with haplotype 23-36-13. Five unknown mutations were associated with different haplotypes for microsatellite markers, whereas three shared the same haplotype. Most delta F508 mutations and all unidentified mutations originated from regions of old and dense settlement in the coastal regions, whereas 394delTT was geographically clustered and enriched in a rural location, consistent with a local founder effect. The remote location of Finland and her population history give a plausible explanation for the rarity of CF in Finland.
authors.affiliation: Department of Medical Genetics, University of Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Kere
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: M
authors.initials: M
authors.lastname: Chillón
authors.forename: N
authors.initials: N
authors.lastname: Morral
authors.forename: V
authors.initials: V
authors.lastname: Nunes
authors.forename: R
authors.initials: R
authors.lastname: Norio
authors.forename: E
authors.initials: E
authors.lastname: Savilahti
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005387:Finland / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator