title: Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes.
abstract: OBJECTIVE
  Several lines of evidence suggest a role for the epithelial sodium channel (ENaC) in cystic fibrosis (CF). The purpose of our study was to assess the contribution of genetic variants in the ENaC subunits (α, β, γ) in nonwhite CF patients in whom CFTR molecular testing has been non-diagnostic.
  
  
  METHODS
  Samples were obtained from patients who were nonwhite and whose molecular CFTR testing did not identify two mutations. Sequencing of the SCNN1A, B, and G genes was performed and variants assessed for pathogenicity and association with CF using databases, protein and splice site mutation analysis software, and literature review.
  
  
  RESULTS
  We identified four nonsynonymous amino acid variants in SCNN1A, three in SCNN1B and one in SCNN1G. There was no convincing evidence of pathogenicity. Whereas all have been reported in the dbSNP database, only p.Ala334Thr, p.Val573Ile, and p.Thr663Ala in SCNN1A, p.Gly442Val in SCNN1B and p.Gly183Ser in SCNN1G were previously reported in ENaC genetic studies of CF or CF-like patients. Synonymous substitutions were also observed but novel synonymous variants were not detected.
  
  
  CONCLUSIONS
  There is no conclusive association of ENaC genetic variants with CF in nonwhite CF patients.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Brennan
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Pique
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94305, USA. Electronic address: ischrijver@stanfordmed.org.
authors.forename: Iris
authors.initials: I
authors.lastname: Schrijver
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D001213:Asian / Q000235:genetics; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D017136:Ion Transport / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020545:Respiratory Mucosa / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; C507045:SCNN1A protein, human; C507048:SCNN1B protein, human; C507052:SCNN1G protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium
keywords: CF; CFTR; Cystic fibrosis; ENaC; Epithelial sodium channel; Molecular diagnosis; Nonwhite; SCNN1