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

被引：62

作者：

Chen, Shitao ^{[1
]}

Wang, Guishuan ^{[2
]}

Zheng, Xiaoguo ^{[1
]}

Ge, Shunna ^{[1
]}

Dai, Yubing ^{[1
]}

Ping, Ping ^{[3
]}

Chen, Xiangfeng ^{[3
]}

Liu, Guihua ^{[4
]}

Zhang, Jing ^{[4
]}

Yang, Yang ^{[5
]}

Zhang, Xinzong ^{[6
]}

Zhong, An ^{[6
]}

Zhu, Yongtong ^{[7
]}

Chu, Qingjun ^{[7
]}

Huang, Yonghan ^{[8
]}

Zhang, Yong ^{[9
]}

Shen, Changli ^{[10
]}

Yuan, Yiming ^{[11
]}

Yuan, Qilong ^{[12
]}

Pei, Xiuying ^{[13
]}

Cheng, C. Yan ^{[14
]}

Sun, Fei ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Sch Med, Shanghai Key Lab Reprod Med, Shanghai 200030, Peoples R China

[2] Nantong Univ, Sch Med, Inst Reprod Med, Nantong 226001, Peoples R China

[3] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Urol,Shanghai Human Sperm Bank, Shanghai 200120, Peoples R China

[4] Sun Yat Sen Univ, Reprod Med Res Ctr, Dept Androl, Affiliated Hosp 6, Guangzhou 510655, Peoples R China

[5] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Dept Reprod, Beijing 100026, Peoples R China

[6] Family Planning Res Inst Guangdong Prov, Key Lab Male Reprod & Genet, Natl Hlth & Family Planning Commiss, Guangzhou 510031, Peoples R China

[7] Southern Med Univ, Nanfang Hosp, Reprod Med Ctr, Dept Obstet & Gynecol, Guangzhou 510515, Peoples R China

[8] Sun Yat Sen Univ, Peoples Hosp Foshan 1, Foshan 528000, Peoples R China

[9] Peoples Liberat Army Gen Hosp, Ctr Assisted Reprod Med, Med Ctr 6, Beijing 100083, Peoples R China

[10] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Reprod Ctr, Guangzhou 510120, Peoples R China

[11] Peking Univ, Hosp Androl Ctr & Urol Dept 1, Beijing 100034, Peoples R China

[12] Guangdong Prov Hosp Chinese Med, Guangzhou 510140, Peoples R China

[13] Ningxia Med Univ, Sch Basic Med, Key Lab Fertil Preservat & Maintenance, Minist Educ, Yinchuan 750004, Ningxia, Peoples R China

[14] Ctr Biomed Res, Mary M Wohlford Lab Male Contracept Res, Populat Council, New York, NY 10065 USA

来源：

HUMAN MOLECULAR GENETICS | 2020年 / 29卷 / 14期

基金：

中国国家自然科学基金;

关键词：

MEIOTIC ARREST; MUTATION; ASSOCIATION; BROMODOMAIN; GUIDELINES; GENETICS; MEN;

D O I：

10.1093/hmg/ddaa101

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2451 / 2459

页数：9

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