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, Abul Kalam Azad, Catherine Verhaeghe, Karin Segers, Jean François Vanbellinghen, Louis Ngendahayo, Emmanuel Kamanzi Rusingiza, Philippe Rutwaza Mutwa, Stephen Rulisa, Lucien Koulischer, Jean Jacques Cassiman, Harry Cuppens, Vincent Bours

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1233-1242
Number of pages10
JournalChest
Volume135
Issue number5
DOIs
StatePublished - May 1 2009
Externally publishedYes

Keywords

  • Africa
  • Cystic fibrosis
  • Cystic fibrosis transmembrane conductance regulator mutations
  • Epithelial sodium channel mutations

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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