Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease

Azad AK, Rauh R, Vermeulen F, Jaspers M, Korbmacher J, Boissier B, Bassinet L, Fichou Y, Des Georges M, Stanke F, De Boeck K, Dupont L, Balascakova M, Hjelte L, Lebecque P, Radojkovic D, Castellani C, Schwartz M, Stuhrmann M, Schwarz M, Skalicka V, De Monestrol I, Girodon E, Ferec C, Claustres M, Tuemmler B, Cassiman JJ, Korbmacher C, Cuppens H (2009)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 2009

Journal

Human Mutation Wiley-Blackwell

Publisher: Wiley-Blackwell

Pages Range: 1093-103

Journal Issue: 30(7)

DOI: 10.1002/humu.21011

Abstract

We investigated whether mutations in the genes that code for the different subunits of the amiloride-sensitive epithelial sodium channel (ENaC) might result in cystic fibrosis (CF)-like disease. In a small fraction of the patients, the disease could be potentially explained by an ENaC mutation by a Mendelian mechanism, such as p.V114I and p.F61L in SCNN1A. More importantly, a more than three-fold significant increase in incidence of several rare ENaC polymorphisms was found in the patient group (30% vs. 9% in controls), indicating an involvement of ENaC in some patients by a polygenetic mechanism. Specifically, a significantly higher number of patients carried c.-5515G > C or p.W493R in SCNN1A in the heterozygous state, with odds ratios (ORs) of 13.5 and 2.7, respectively. The p.W493R-SCNN1A polymorphism was even found to result in a four-fold more active ENaC channel when heterologously expressed in Xenopus laevis oocytes. About 1 in 975 individuals in the general population will be heterozygous for the hyperactive p.W493R-SCNN1A mutation and a cystic fibrosis transmembrane conductance regulator (CFTR) gene that results in very low amounts (0-10%) functional CFTR. These ENaC/CFTR genotypes may play a hitherto unrecognized role in lung diseases. © 2009 Wiley-Liss, Inc.

Authors with CRIS profile

Robert Rauh Lehrstuhl für Physiologie (Vegetative Physiologie) Judit Korbmacher Medizinische Fakultät Christoph Korbmacher Lehrstuhl für Physiologie (Vegetative Physiologie)

Involved external institutions

University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven BE Belgium (BE) University of Montpellier / Université Montpellier FR France (FR) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Rigshospitalet DK Denmark (DK) University Hospital of Verona / Azienda Ospedaliera Universitaria Integrata Verona (AOUI) IT Italy (IT) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ) Karolinska University Hospital / Karolinska Universitetssjukhuset SE Sweden (SE) Centre hospitalier universitaire Henri-Mondor (CHU Henri-Mondor) FR France (FR) Centre hospitalier universitaire de Brest (CHRU Brest) FR France (FR) Université Catholique de Louvain (UCL) BE Belgium (BE)

How to cite

APA:

Azad, A.K., Rauh, R., Vermeulen, F., Jaspers, M., Korbmacher, J., Boissier, B.,... Cuppens, H. (2009). Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Human Mutation, 30(7), 1093-103. https://doi.org/10.1002/humu.21011

MLA:

Azad, Abul Kalam, et al. "Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease." Human Mutation 30(7) (2009): 1093-103.

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