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Congenital absence of the vas deferens (CAVD), a congenital malformation of the male reproductive system, causes obstructive azoospermia and male infertility. Currently, the cystic fibrosis transmembrane conductance regulator (CFTR) has been recognized as the main pathogenic gene in CAVD, with some other genes, such as adhesion G-protein-coupled receptor G2 (ADGRG2), solute carrier family 9 isoform 3 (SLC9A3), sodium channel epithelial 1 subunit beta (SCNN1B), and carbonic anhydrase 12 (CA12), being candidate genes in the pathogenesis of CAVD. However, the frequency and spectrum of these mutations, as well as the pathogenic mechanisms of CAVD, have not been fully investigated. Here, we sequenced all genes with potentially pathogenic mutations using next-generation sequencing and verified all identified variants by Sanger sequencing. Further bioinformatic analysis was performed to predict the pathogenicity of mutations. We described the distribution of the p.V470M, poly-T, and TG-repeat CFTR polymorphisms and identified novel missense mutations in the CFTR and SLC9A3 genes, respectively. Taken together, we identified mutations in the CFTR, ADGRG2, SLC9A3, SCNN1B, and CA12 genes in 22 patients with CAVD, thus broadening the genetic spectrum of Chinese patients with CAVD.

Congenital bilateral absence of the vas deferens (CBAVD) is a congenital malformation of the male reproductive system and one of the important causes of obstructive azoospermia and male infertility. It is currently recognized that the main cause of CBAVD is the mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR). And the mutations of adhesion G protein-coupled receptor G2 (ADGRG2), solute carrier family 9 isoform 3 (SLC9A3) and other genes are also found to be involved in the development and progression of CBAVD. A reasonable CBAVD molecular diagnosis process combined with assisted reproductive technology is currently the most effective method for the diagnosis and treatment of CBAVD, but the offspring of the patient may face the risk of hereditary inheritance. This article focuses on the pathogenesis of CFTR, ADGRG2 and SLC9A3 causing CBAVD, and aims to provide some new ideas for the clinical diagnosis and treatment of CBAVD and CBAVD-related genetic counseling.