Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes

作者：Shitao Chen, Guishuan Wang, Xiaoguo Zheng, Shunna Ge, Yubing Dai, Ping Ping, Xiangfeng Chen, Guihua Liu, Jing Zhang, Yang Yang, Xinzong Zhang, An Zhong, Yongtong Zhu, Qingjun Chu, Yonghan Huang, Yong Zhang, Changli Shen, Yiming Yuan, Qilong Yuan, Xiuying Pei, C. Yan Cheng, Fei Sun · 发表于：Human Molecular Genetics · 年份：2020 · DOI：10.1093/hmg/ddaa101 · 被引用次数：79 · 研究领域：Sperm and Testicular Function、Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities、Urologic and reproductive health conditions

Rare coding variants have been proven to be one of the significant factors contributing to spermatogenic failure in patients with non-obstructive azoospermia (NOA) and severe oligospermia (SO). To delineate the molecular characteristics of idiopathic NOA and SO, we performed whole-exome sequencing of 314 unrelated patients of Chinese Han origin and verified our findings by comparing to 400 fertile controls. We detected six pathogenic/likely pathogenic variants and four variants of unknown significance, in genes known to cause NOA/SO, and 9 of which had not been earlier reported. Additionally, we identified 20 novel NOA candidate genes affecting 25 patients. Among them, five (BRDT, CHD5, MCM9, MLH3 and ZFX) were considered as strong candidates based on the evidence obtained from murine functional studies and human single-cell (sc)RNA-sequencing data. These genetic findings provide insight into the aetiology of human NOA/SO and pave the way for further functional analysis and molecular diagnosis of male infertility.