title: Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials.
abstract: OBJECTIVE
  To examine the relationship between cystic fibrosis transmembrane regulator gene mutations (CFTR) and in vivo transepithelial potentials.
  
  
  METHODS
  We prospectively evaluated 162 men including 31 healthy subjects, 21 obligate heterozygotes, 60 with congenital bilateral absence of the vas deferens (CBAVD) and 50 with CF by extensive CFTR genotyping, sweat chloride and nasal potential difference testing.
  
  
  RESULTS
  Six (10%) men with CBAVD carried no CFTR mutations, 18 (30%) carried one mutation, including the 5T variant, and 36 (60%) carried mutations on both alleles, for a significantly higher rate carrying one or more mutations than healthy controls (90% versus 19%, p < 0.001). There was an overlapping spectrum of ion channel measurements among the men with CBAVD, ranging from values in the control and obligate heterozygote range at one extreme, to values in the CF range at the other. All pancreatic-sufficient patients with CF and 34 of 36 patients with CBAVD with mutations on both alleles carried at least one mild mutation. However, the distribution of mild mutations in the two groups differed greatly. Genotyping, sweat chloride and nasal potential difference (alone or in combination) excluded CF in all CBAVD men with no mutations. CF was confirmed in 56% and 67% of CBAVD men carrying 1 and 2 CFTR mutations, respectively.
  
  
  CONCLUSIONS
  Abnormalities of CFTR transepithelial function correlate with the number and severity of CFTR gene mutations.
authors.affiliation: The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilschanski
authors.forename: Annie
authors.initials: A
authors.lastname: Dupuis
authors.forename: Lynda
authors.initials: L
authors.lastname: Ellis
authors.forename: Keith
authors.initials: K
authors.lastname: Jarvi
authors.forename: Julian
authors.initials: J
authors.lastname: Zielenski
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
authors.forename: Sheelagh
authors.initials: S
authors.lastname: Martin
authors.forename: Mary
authors.initials: M
authors.lastname: Corey
authors.forename: Lap-Chee
authors.initials: LC
authors.lastname: Tsui
authors.forename: Peter
authors.initials: P
authors.lastname: Durie
mesh_terms: D000483:Alleles; D000584:Amiloride / Q000494:pharmacology; D002712:Chlorides / Q000032:analysis; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008297:Male; D009666:Nose / Q000166:cytology; D011446:Prospective Studies; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013542:Sweat / Q000737:chemistry; D014649:Vas Deferens / Q000002:abnormalities / Q000378:metabolism
chemical_list: D002712:Chlorides; D026941:Sodium Channel Blockers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride