Congenital absence of the vas deferens: Incomplete penetrance of cystic fibrosis gene mutations

Purpose: We evaluated the penetrance of cystic fibrosis gene mutations for the Materials and Methods: We retrospectively reviewed the fertility status of 244 brothers of 105 men with congenital bilateral absence of the vas deferens. Testing for the most; common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and for haplotype analysis of the intron 8/polythymidine segment was recommended for all men with congenital bilateral absence of the vas deferens. Results: Of 244 brothers of men with congenital bilateral absence of the vas deferens 131 were eligible for assessment of fertility. Of the 131 evaluable brothers only 7 (5%) were found to have congenital bilateral absence of the vas deferens. This prevalence is 5 times lower than that predicted for congenital bilateral absence of the vas deferens (25%) based on the autosomal recessive inheritance pattern seen in classical cystic fibrosis. For couples in which the man has congenital bilateral absence of the vas deferens and the female partner tests negative for standard CFTR gene mutations including 5T analysis, the maximum risk of having a child with congenital bilateral absence of the vas deferens is less than 1.0%. Conclusions: Our data are consistent with incomplete penetrance for the congenital bilateral absence of the vas deferens phenotype after inheritance of cystic fibrosis gene mutations, even after adjusting for environmental factors and wolffian anomalies. Incomplete penetrance may account for a low prevalence of congenital bilateral absence of the vas deferens in the population and may lower the risk of having a child with congenital bilateral absence of the vas deferens for couples undergoing sperm retrieval and assisted reproductive techniques.