title: Frequency of the hyperactive W493R ENaC variant in carriers of a CFTR mutation.
abstract: BACKGROUND
  The basic defect of the autosomal recessive disorder cystic fibrosis (CF) manifests in chloride hyposecretion and sodium hyperabsorption. CF-like disease has been reported in a heterozygous carrier of F508del CFTR and the hyperactive variant p.W493R-SCNN1A of the epithelial sodium channel (ENaC).
  
  
  METHODS
  The hypothesis that heterozygosity for p.W493R-SCNN1A and one loss-of-function CFTR mutation causes or predisposes to CF or CF-like disease was tested in 441 parents of a child with CF.
  
  
  RESULTS
  p.W493R-SCNN1A was detected in three female carriers of F508del CFTR who did not show any symptoms of respiratory or intestinal disease that could be interpreted as the manifestation of CF or CFTR-related disorder. Frequency of p.W493R was lower in CF parents than in Caucasian control subjects.
  
  
  CONCLUSIONS
  A hyperactive ENaC does not necessarily cause CF-like disease in a CF gene carrier, but its low frequency in CF parents suggests that it is a risk factor.
authors.affiliation: Klinische Forschergruppe‚ Molekulare Pathologie der Mukoviszidose‘, Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Handschick
authors.forename: Silke
authors.initials: S
authors.lastname: Hedtfeld
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics*; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male
chemical_list: D053503:Epithelial Sodium Channels