title: Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants.
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 alpha (SCNN1A), sodium channel non-voltage-gated 1 beta (SCNN1B), and sodium channel non-voltage-gated 1 gamma (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.
  
  
  CONCLUSIONS
  Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations.
authors.affiliation: Department of Human Genetics, Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium.
authors.forename: Léon
authors.initials: L
authors.lastname: Mutesa
authors.affiliation: Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Azad
authors.affiliation: Department of Human Genetics, Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Verhaeghe
authors.affiliation: Department of Human Genetics, Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Segers
authors.affiliation: Department of Human Genetics, Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Vanbellinghen
authors.affiliation: Department of Pathology, Centre Hospitalier Universitaire-Butare, National University of Rwanda, Butare, Rwanda.
authors.forename: Louis
authors.initials: L
authors.lastname: Ngendahayo
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire-Kigali, National University of Rwanda, Kigali, Rwanda.
authors.forename: Emmanuel Kamanzi
authors.initials: EK
authors.lastname: Rusingiza
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire-Kigali, National University of Rwanda, Kigali, Rwanda.
authors.forename: Philippe Rutwaza
authors.initials: PR
authors.lastname: Mutwa
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire-Kigali, National University of Rwanda, Kigali, Rwanda.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rulisa
authors.affiliation: Department of Human Genetics, Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium.
authors.forename: Lucien
authors.initials: L
authors.lastname: Koulischer
authors.affiliation: Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Cassiman
authors.affiliation: Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Harry
authors.initials: H
authors.lastname: Cuppens
authors.affiliation: Department of Human Genetics, Centre Hospitalier Universitaire-Sart-Tilman, Grappe Interdisciplinaire de Genoprotéomique Appliquée-Research, University of Liège, Liège, Belgium. Electronic address: vbours@ulg.ac.be.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
mesh_terms: D000293:Adolescent; D044383:Black People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012432:Rwanda
chemical_list: D053503:Epithelial Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator