Genetic mutation analysis of 22 patients with congenital absence of vas deferens: a single-center study†

Biol Reprod. 2022 Jan 13;106(1):108-117. doi: 10.1093/biolre/ioab194.


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.

Keywords: adhesion G-protein-coupled receptor G2; carbonic anhydrase 12; congenital absence of the vas deferens; cystic fibrosis transmembrane conductance regulator; sodium channel epithelial 1 subunit beta; solute carrier family 9 isoform 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Azoospermia / genetics
  • China
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • DNA Mutational Analysis
  • Epithelial Sodium Channels / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infertility, Male / genetics
  • Male
  • Male Urogenital Diseases / genetics*
  • Mutation*
  • Mutation, Missense
  • Polymorphism, Genetic
  • Receptors, G-Protein-Coupled / genetics
  • Sequence Analysis, DNA
  • Sodium-Hydrogen Exchanger 3 / genetics
  • Vas Deferens / abnormalities*


  • ADGRG2 protein, human
  • CFTR protein, human
  • Epithelial Sodium Channels
  • Receptors, G-Protein-Coupled
  • SCNN1B protein, human
  • SLC9A3 protein, human
  • Sodium-Hydrogen Exchanger 3
  • Cystic Fibrosis Transmembrane Conductance Regulator

Supplementary concepts

  • Congenital bilateral aplasia of vas deferens