Genetic, andrological and clinical characteristics of patients with congenital bilateral absence of the vas deferens

The possibility of retrieving spermatozoa from the epididymis allows patien ts with congenital bilateral absence of the vas deferens (CBAVD) to father a child by means of assisted reproduction techniques. This has, however, in creased the chance of transmitting a mutated allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene which increases the risk of generating offspring with cystic fibrosis (CF). Because of the increased h eterogeneity of the CFTR locus, the study of a discrete number of mutations , as usually carried out in a diagnostic work-up, is unable to ascertain th e presence of a mutation in a relatively high proportion of the patients sc reened. In an attempt to increase the chance of detecting the presence of C FTR gene abnormalities, 37 patients with CBAVD and one patient with congeni tal unilateral agenesis of the vas deferens (CUAVD) underwent an enlarged d iagnostic protocol, which included screening for the most expected mutation s of the CFTR gene in our population, evaluation of the five thymidine (5T) allelic variant, sweat test, respiratory function tests, evaluation of ste atocrit, and an accurate evaluation of the history of the patient to search for symptoms commonly found in patients with CF. A single CFTR gene mutati on was found in 18 patients (48.6%) with CBAVD and in the patient with CUAV D. The most frequent mutation observed was the Delta F508. Eleven patients (45.8%) had the 5T variant and in five of them it was not associated with a ny detectable mutation of the CFTR gene. Two female partners were found to be carriers of a mutation, whereas 5 (18.5%) had the 5T variant. As many as 71% of CBVAD patients had the simultaneous presence of at least two signs and/or symptoms suggestive of CF, albeit they were of mild intensity and th e patients felt fit and healthy. In conclusion, these results suggested tha t some patients with CBAVD without CFTR gene mutation or 5T variant, even w hen their sweat test is negative, may show clinical suspicion of carrying a CFTR gene mutation and therefore are at risk of generating children affect ed by CF if the partner carries a mutation as well. The screening for mutat ions and a careful clinical examination may contribute to better identifica tion of patients with CFTR-related CBAVD.