Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes

作者：Brennan Marie Luise; Pique Lynn M; Schrijver Iris^*

来源：Journal of Cystic Fibrosis, 2016, 15(1): 52-59.

DOI：10.1016/j.jcf.2015.04.001

• Cystic fibrosis
• CF
• Epithelial sodium channel
• ENaC
• SCNN1
• Molecular diagnosis
• CFTR
• Nonwhite

Purpose: 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 (alpha, beta, gamma) 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.
Conclusion: There is no conclusive association of ENaC genetic variants with CF in nonwhite CF patients.

• 出版日期2016-1