Landscape of pathogenic mutations in premature ovarian insufficiency

doi:10.1038/s41591-022-02194-3

	Landscape of pathogenic mutations in premature ovarian insufficiency
	Ke, Hanni 1,2; Tang, Shuyan 3; Guo, Ting 1,2; Hou, Dong 1,2; Jiao, Xue 1,2; Li, Shan 1,2; Luo, Wei 1,2; Xu, Bingying 1,2; Zhao, Shidou 1,2; Li, Guangyu 1,2; Zhang, Xiaoxi4 ; Xu, Shuhua4,5 ; Wang, Lingbo 3; Wu, Yanhua 5; Wang, Jiucun 5,9; Zhang, Feng 3,5,6; Qin, Yingying 1,2; Jin, Li 5,9; Chen, Zi-Jiang 1,2,7,8
	2023-02-01
发表期刊	NATURE MEDICINE;
ISSN	1078-8956
EISSN	1546-170X
卷号	29 期号:2 页码:483-492
DOI	10.1038/s41591-022-02194-3
摘要	Premature ovarian insufficiency (POI) is a major cause of female infertility due to early loss of ovarian function. POI is a heterogeneous condition, and its molecular etiology is unclear. To identify genetic variants associated with POI, here we performed whole-exome sequencing in a cohort of 1,030 patients with POI. We detected 195 pathogenic/likely pathogenic variants in 59 known POI-causative genes, accounting for 193 (18.7%) cases. Association analyses comparing the POI cohort with a control cohort of 5,000 individuals without POI identified 20 further POI-associated genes with a significantly higher burden of loss-of-function variants. Functional annotations of these novel 20 genes indicated their involvement in ovarian development and function, including gonadogenesis (LGR4 and PRDM1), meiosis (CPEB1, KASH5, MCMDC2, MEIOSIN, NUP43, RFWD3, SHOC1, SLX4 and STRA8) and folliculogenesis and ovulation (ALOX12, BMP6, H1-8, HMMR, HSD17B1, MST1R, PPM1B, ZAR1 and ZP3). Cumulatively, pathogenic and likely pathogenic variants in known POI-causative and novel POI-associated genes contributed to 242 (23.5%) cases. Further genotype–phenotype correlation analyses indicated that genetic contribution was higher in cases with primary amenorrhea compared to that in cases with secondary amenorrhea. This study expands understanding of the genetic landscape underlying POI and presents insights that have the potential to improve the utility of diagnostic genetic screenings.
学科门类	Biochemistry, Genetics and Molecular Biology (all)
URL	查看原文
收录类别	SCOPUS
语种	英语
原始文献类型	Article
Scopus 记录号	2-s2.0-85147268746
来源库	SCOPUS
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286536
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_徐书华组生命科学与技术学院_博士生
作者单位	1.Center for Reproductive Medicine,Cheeloo College of Medicine,Shandong University,Jinan,China; 2.Key Laboratory of Reproductive Endocrinology of Ministry of Education,National Research Center for Assisted Reproductive Technology and Reproductive Genetics,Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Clinical Research Center for Reproductive Health,Jinan,China; 3.Obstetrics and Gynecology Hospital,Institute of Reproduction and Development,Fudan University,Shanghai,China; 4.School of Life Science and Technology,ShanghaiTech University,Shanghai,China; 5.State Key Laboratory of Genetic Engineering,School of Life Sciences,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Fudan University,Shanghai,China; 6.Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases,Shanghai,China; 7.Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics,Shanghai,China; 8.Center for Reproductive Medicine,Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China; 9.Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058),Chinese Academy of Medical Sciences,Shanghai,China
推荐引用方式 GB/T 7714	Ke, Hanni,Tang, Shuyan,Guo, Ting,et al. Landscape of pathogenic mutations in premature ovarian insufficiency[J]. NATURE MEDICINE;,2023,29(2):483-492.
APA	Ke, Hanni.,Tang, Shuyan.,Guo, Ting.,Hou, Dong.,Jiao, Xue.,...&Chen, Zi-Jiang.(2023).Landscape of pathogenic mutations in premature ovarian insufficiency.NATURE MEDICINE;,29(2),483-492.
MLA	Ke, Hanni,et al."Landscape of pathogenic mutations in premature ovarian insufficiency".NATURE MEDICINE; 29.2(2023):483-492.