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Original Research: CYSTIC FIBROSIS |

Genetic Analysis of Rwandan Patients With Cystic Fibrosis-Like Symptoms: Identification of Novel Cystic Fibrosis Transmembrane Conductance Regulator and Epithelial Sodium Channel Gene Variants

Léon Mutesa, MD; Abul Kalam Azad, MD; Catherine Verhaeghe, PhD; Karin Segers, PhD; Jean-François Vanbellinghen, MSc; Louis Ngendahayo, MD; Emmanuel Kamanzi Rusingiza, MD; Philippe Rutwaza Mutwa, MD; Stephen Rulisa, MD; Lucien Koulischer, MD, PhD; Jean-Jacques Cassiman, MD, PhD; Harry Cuppens, PhD; Vincent Bours, MD, PhD
Author and Funding Information

*From the Department of Human Genetics (Drs. Mutesa, Verhaeghe, Segers, Koulischer, and Bours, and Mr. Vanbellinghen), Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium; the Department of Human Genetics (Drs. Azad, Cassiman, and Cuppens), Katholieke Universiteit Leuven, Leuven, Belgium; the Department of Pathology (Dr. Ngendahayo), Centre Hospitalier Universitaire-Butare, National University of Rwanda, Butare, Rwanda; and the Department of Pediatrics (Drs. Rusingiza, Mutwa, and Rulisa), Centre Hospitalier Universitaire-Kigali, National University of Rwanda, Kigali, Rwanda.

Correspondence to: Vincent Bours, MD, PhD, Department of Human Genetics, CHU Sart-Tilman, University of Liège, 4000 Liège, Belgium; e-mail: vbours@ulg.ac.be


This work was supported by grants from the Commission Universitaire au Development (CUD), the Fondation Léon Frédéricq (University of Liège and Centre Hospitalier Universitaire-Liège), the “Alphonse and Jean Forton Fund–Koning Boudewijn Stichting” (grant 2005 04 R7 115 BO), “Het Fonds voor Wetenschappelijk Onderzoek Vlaanderen” (grants G.0521.06 and 1.5.111.07), and the Interuniversity Attraction Poles (IAP P6/05). Dr. Mutesa was a recipient of doctoral fellowship grant from the “Conseil Interuniversitaire de la Communauté Française.” Dr. Cassiman is the holder of the Arthur Bax and Anna Vanluffelen Chair of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(5):1233-1242. doi:10.1378/chest.08-2246
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Background:  The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CF transmembrane conductance regulator (CFTR) loss of function and an abnormal interaction between CFTR and the epithelial sodium channel (ENaC). A few patients were described with CF-like symptoms, a single CFTR mutation, and an ENaC mutation.

Methods:  To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes, we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed in all patients by denaturing high-performance liquid chromatography followed by direct sequencing; whereas, the sodium channel non-voltage-gated 1 α (SCNN1A), sodium channel non-voltage-gated 1 β (SCNN1B), and sodium channel non-voltage-gated 1 γ (SCNN1G) subunits of the ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients without any CFTR mutation.

Results:  Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified in five patients. ENaC gene sequencing in these five patients detected the following eight ENaC variants: c.72T>C and p.V573I in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S and c.1176 + 30G>C in SCNN1G. In the 55 CF-like patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism, but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group.

Conclusion:  Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations.

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