TY - JOUR
T1 - Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms
T2 - Identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants
AU - Mutesa, Léon
AU - Azad, Abul Kalam
AU - Verhaeghe, Catherine
AU - Segers, Karin
AU - Vanbellinghen, Jean François
AU - Ngendahayo, Louis
AU - Rusingiza, Emmanuel Kamanzi
AU - Mutwa, Philippe Rutwaza
AU - Rulisa, Stephen
AU - Koulischer, Lucien
AU - Cassiman, Jean Jacques
AU - Cuppens, Harry
AU - Bours, Vincent
N1 - Funding Information:
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.
PY - 2009/5/1
Y1 - 2009/5/1
N2 - 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.
AB - 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.
KW - Africa
KW - Cystic fibrosis
KW - Cystic fibrosis transmembrane conductance regulator mutations
KW - Epithelial sodium channel mutations
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U2 - 10.1378/chest.08-2246
DO - 10.1378/chest.08-2246
M3 - Article
C2 - 19017867
AN - SCOPUS:65949097928
SN - 0012-3692
VL - 135
SP - 1233
EP - 1242
JO - Chest
JF - Chest
IS - 5
ER -