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Data confirm that CFTR+5T mutations represent the most common genetic abnormality in CAVD, and suggest that cases of NOAZ may be associated with the 5T allele.

Purpose: Approximately 20% of patients with congenital absence of the vas deferens remain without two mutations identified. We applied a strategy of serial screening steps to 45 patients with congenital absence of the vas deferens and characterized cystic fibrosis transmembrane conductance regulator gene mutations in all cases.Methods: DNA samples of 45 patients with congenital absence of the vas deferens were screened by successive different molecular genetics approaches. Results: Initial screening for the 31 most frequent cystic fibrosis mutations, IVS8 poly(TG)m, poly(T)n, and M470V polymorphisms, identified 8 different mutations in 40 patients (88.9%). Extensive cystic fibrosis transmembrane conductance regulator gene analysis by denaturing gradient gel electrophoresis, denaturing high-performance liquid chromatography, and DNA sequencing detected 17 further mutations, of which three were novel. Cystic fibrosis transmembrane conductance regulator gene rearrangements were searched by semiquantitative fluorescent multiplex polymerase chain reaction, which detected a CFTRdele2,3 (21 kb) large deletion and confirmed two homozygous mutations. Overall, 42 patients (93.3%) had two mutations and 3 patients (6.7%) had one mutation detected. Conclusions: The present screening strategy allowed a higher mutation detection rate than previous studies, with at least one cystic fibrosis transmembrane conductance regulator gene mutation found in all patients with congenital absence of the vas deferens. Genet Med 2007:9(3):163-172. Key Words: CAVD, CBAVD, CUAVD, CFTR mutations, CFTR rearrangements, cystic fibrosis, male infertilityCongenital absence of the vas deferens (CAVD) in otherwise healthy males is responsible for 1% to 2% of male infertility and 6% of obstructive azoospermia cases. The disease was classified as a primary genital form of cystic fibrosis (CF) because 67% to 85% of patients with CAVD have mutations and/or splicing variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CAVD with upper urinary tract malformations (20% of cases) have a normal frequency of CFTR mutations and are thus considered a distinct clinical entity with a different cause. [1][2][3][4][5][6][7][8] CFTR genotypes in patients with CAVD are markedly different from those found in patients with CF. Patients with CAVD are usually heterozygous for a mild mutation on one allele and a severe mutation on the second allele (88%), or for mild mutations on both CFTR alleles (12%). On the other hand, homozygosity or compound heterozygosity for two severe mutations is responsible for the classic CF phenotype. The most common CFTR mutations found in CAVD are T5 allele, deltaF508, and R117H, with the combination between the T5 allele and a severe CF mutation in the other allele being the main cause of CAVD. 9 The polymorphic polythymidine locus (Tn) is located within the 3= splice acceptor site of intron 8 (IVS8 poly[T]n). The length of the IVS8 poly(T)n tract (T5/T7/T9) is inversely correlated with the degree of ...