title: Nasal epithelial ion transport and genetic analysis of infertile men with congenital bilateral absence of the vas deferens.
abstract: It has been suggested that congenital bilateral absence of the vas deferens (CBAVD), an important cause of male infertility, is a variant of cystic fibrosis (CF). This study describes a defect in chloride conductance across the nasal epithelium of subjects with CBAVD which is dissimilar to that found in patients with CF. It also demonstrates normal sodium transport across the nasal epithelium in these men, in contrast to patients with CF who exhibit increased sodium absorption. The increased frequency of CFTR mutations in these men implicates the CFTR gene in the pathogenesis of this disorder. Genetic analysis of men with CBAVD who were heterozygous for a known CFTR mutation failed to identify a second mutation within any of the exons or introns of the CFTR gene. These results demonstrate that most men presenting with CBAVD are not compound heterozygotes for mutations within the CFTR gene and can be distinguished from individuals with atypical or asymptomatic CF on the basis of the bioelectric properties of their nasal epithelium. We postulate that mutations in the promoter region or at other regulatory sites of the CFTR gene may be responsible for the CBAVD phenotype in a proportion of cases.
authors.affiliation: Department of Cystic Fibrosis, National Heart and Lung Institute, London, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Osborne
authors.forename: M
authors.initials: M
authors.lastname: Lynch
authors.forename: P G
authors.initials: PG
authors.lastname: Middleton
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: J P
authors.initials: JP
authors.lastname: Pryor
authors.forename: M E
authors.initials: ME
authors.lastname: Hodson
authors.forename: G K
authors.initials: GK
authors.lastname: Santis
mesh_terms: D001692:Biological Transport; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009297:Nasal Mucosa / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D012964:Sodium / Q000378:metabolism; D013542:Sweat / Q000737:chemistry; D014649:Vas Deferens / Q000002:abnormalities*
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium