• PMID: 28805948
• Gene Name: ADGRG2
• Condition: Congenital bilateral absence of the vas deferens (CBAVD), Male infertility
• Association: Associated
• Mutation: c.G1709A, p.C570Y; and c.A2968G, p.K990E
• Population size: 18 CBAVD patients
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Congenital bilateral absence of the vas deferens (CBAVD), Male infertility

Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population

Yang B, Wang J, Zhang W, Pan H, Li T, Liu B, Li H, Wang B.

Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of obstructive azoospermia and male infertility worldwide. Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are the main pathogenic cause, although a proportion of cases are still unexplained. Recently, adhesion G protein-coupled receptor G2 (ADGRG2) gene, a novel pathogenic gene for CBAVD was identified. We did a single population replication study in Chinese CBAVD patients to replicate its role in CBAVD developing. In this study, we performed whole-exome sequencing in 18 unrelated CBAVD patients and identified two missense variants in two patients (c.G1709A, p.C570Y; and c.A2968G, p.K990E). Both variants were predicted to be deleterious and highly conserved in silico. The p.C570Y variant is located in the G protein-coupled receptor (GPCR) proteolysis site domain, which is functionally necessary for autoproteolysis, while the p.K990E variant is in the N-terminal fragment that may regulate activity of the adhesion GPCR. We did not find any potential pathogenic CFTR variants, implying the ADGRG2 variants are the genetic cause in these patients. To the best of our knowledge, these are the first two ADGRG2 variants to be identified in Chinese CBAVD patients, which further validate the disease-causing role of ADGRG2 in this congenital defect. CI - © 2017 American Society of Andrology and European Academy of Andrology. FAU - Yang, B AU - Yang B AD - Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Wang, J AU - Wang J AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. FAU - Zhang, W AU - Zhang W AD - Center for Genetics, National Research Institute for Family Planning, Beijing, China. AD - Graduate School of Peking Union Medical College, Beijing, China. FAU - Pan, H AU - Pan H AD - Center for Genetics, National Research Institute for Family Planning, Beijing, China. AD - Graduate School of Peking Union Medical College, Beijing, China. FAU - Li, T AU - Li T AD - Center for Genetics, National Research Institute for Family Planning, Beijing, China. FAU - Liu, B AU - Liu B AD - Center for Genetics, National Research Institute for Family Planning, Beijing, China. FAU - Li, H AU - Li H AD - Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.