Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling

BACKGROUND: Mutations in the cystic fibrosis (CF) transmembrane conductanceregulator (CFTR) gene have been widely detected in infertilemen with congenital bilateral absence of the vas deferens (CBAVD).Despite extensive analysis of the CFTR gene using varied screeningmethods, a number of cases remain unsolved and could be attributableto the presence of large gene rearrangements, as recently shownfor CF patients. METHODS: We carried out a complete CFTR gene study in a group of 222CBAVD patients with strict diagnosis criteria and without renalanomaly, and searched for rearrangements using a semi-quantitativeassay in a subgroup of 61 patients. RESULTS: The overall mutation detection rate was 87.8%, and 82% of patientscarried two mutations. Ten out of the 99 different mutationsaccounted for 74.6% of identified alleles. Four large rearrangementswere found in patients who already carried a mild mutation:two known partial deletions (exons 17a to 18 and 22 to 23),a complete deletion and a new partial duplication (exons 11to 13). The rearrangements accounted for 7% of the previouslyunknown alleles and 1% of all identified alleles. CONCLUSIONS: Screening for rearrangements should be part of comprehensiveCFTR gene studies in CBAVD patients and may have impacts ongenetic counselling for the patients and their families.