NASAL EPITHELIAL ION-TRANSPORT AND GENETIC-ANALYSIS OF INFERTILE MEN WITH CONGENITAL BILATERAL ABSENCE OF THE VAS-DEFERENS

It has been suggested that congenital bilateral absence of the vas def erens (CBAVD), an important cause of male infertility, is a variant of cystic fibrosis (CF). This study describes a defect in chloride condu ctance across the nasal epithelium of subjects with CBAVD which is dis similar to that found in patients with CF. It also demonstrates normal sodium transport across the nasal epithelium in these men, in contras t to patients with CF who exhibit increased sodium absorption. The inc reased frequency of CFTR mutations in these men implicates the CFTR ge ne in the pathogenesis of this disorder. Genetic analysis of men with CBAVD who were heterozygous for a known CFTR mutation failed to identi fy a second mutation within any of the exons or introns of the CFTR ge ne. 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 reponsible for the CBAVD phenotype in a proportion of cases.