CFTR HAPLOTYPE ANALYSIS REVEALS GENETIC-HETEROGENEITY IN THE ETIOLOGYOF CONGENITAL BILATERAL APLASIA OF THE VAS-DEFERENS

Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the c ystic fibrosis transmembrane conductance regulator (CFTR) gene in male s with CBAVD revealed that in some males CBAVD is caused by two defect ive CFTR alleles. The genetic basis of CBAVD in the other males and it s association with CF remained unclear. We undertook this study to tes t the hypothesis of commonality of CBAVD and CF by haplotype analysis, in the CFTR locus, of males suffering from CBAVD and of their familie s. According to the hypothesis of commonality of CBAVD and CF, two bro thers with CBAVD are expected to carry the same two CFTR alleles, whil e their fertile brothers are expected to carry at least one different allele. Eleven families were studied, of which two families, with unid entified CFTR mutations, did not support this hypothesis. In these fam ilies two brothers with CBAVD inherited different CFTR alleles. Their fertile brothers inherited the same CFTR alleles as their brothers wit h CBAVD. These results provide evidence for genetic heterogeneity in C BAVD. Though in some families CBAVD is associated with two CFTR mutati ons, we suggest that in others it is caused by other mechanisms, such as mutations at other loci or homozygosity or heterozygosity for parti ally penetrant CFTR mutations.