Objective: Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders.
Design: We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms.
Setting: All the patients presented to a male infertility clinic of a teaching hospital.
Subjects: Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry.
Results: Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (P less than .001). Moreover, we have thus far determined that three of these 16 men are compound heterozygotes, one of whom has a mutation not previously described. Analyses continue on patients who have yet to yield a detectable mutation.
Conclusions: Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives.