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Pathogenic role of ADGRG 2 in CBAVD patients replicated in Chinese population
Author(s) -
Yang B.,
Wang J.,
Zhang W.,
Pan H.,
Li T.,
Liu B.,
Li H.,
Wang B.
Publication year - 2017
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12407
Subject(s) - biology , missense mutation , genetics , cystic fibrosis transmembrane conductance regulator , population , exome sequencing , virulence , cystic fibrosis , gene , mutation , medicine , environmental health
Summary 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 ( ADGRG 2 ) 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 ADGRG 2 variants are the genetic cause in these patients. To the best of our knowledge, these are the first two ADGRG 2 variants to be identified in Chinese CBAVD patients, which further validate the disease‐causing role of ADGRG 2 in this congenital defect.