Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia

doi:10.1093/molehr/gaac021

	Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia
	Yang, Chao 1,2; Lin, Xiaoqi 3,4; Ji, Zhiyong 1; Huang, Yuhua 1; Zhang, Ling 5,6; Luo, Jiaqiang 1; Chen, Huixing 1; Li, Peng 1; Tian, Ruhui 1; Zhi, Erlei 1; Hong, Yan 1; Zhou, Zhi7 ; Zhang, Feng 3,4; Li, Zheng 1; Yao, Chencheng 1
	2022-06-30
发表期刊	MOLECULAR HUMAN REPRODUCTION (IF:3.6[JCR-2023],3.9[5-Year])
ISSN	1360-9947
EISSN	1460-2407
卷号	28 期号:7
发表状态	已发表
DOI	10.1093/molehr/gaac021
摘要	KASH5 is an essential component of the LINC (linker of the nucleoskeleton and cytoskeleton) complex that regulates chromosome movements and nuclear envelope (NE) remodeling in mouse spermatocytes during meiosis prophase I, but its expression and function in human cells, as well as its association with male infertility are largely unknown. In this study, a novel heterozygous copy number variation (CNV) (seq [GRCh37] del(19) (19q13.33) chr19: g.49894043-49903011del) and a heterozygous loss of function variant (NM_144688: c.979_980del: p.R327Sfs*21) in human KASH5 were identified in a non-obstructive azoospermia (NOA)-affected patient and in his infertile sister by whole-exome sequencing and CNV array. Spermatogenesis in the proband was arrested at zygotene-like stage with a deficiency in homolog pairing and synapsis. KASH5 protein expression in human spermatocytes was evaluated and reported first in this study. Single-cell RNA sequencing demonstrated that the LINC complex and associated genes in human and mouse shared a similar expression pattern, indicating a conserved mechanism in the regulation of chromosome movements and NE remodeling. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis. Collectively, we have identified novel rare variants within human KASH5 in patients with NOA and meiosis arrest. Our study expands the knowledge of KASH5 and associated proteins in regulating human meiosis prophase I progress and provides new insight into the genetic etiology of NOA.
关键词	KASH5 male infertility meiotic arrest LINC complex meiosis prophase I
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[82171597,81871215]
WOS研究方向	Developmental Biology ; Obstetrics & Gynecology ; Reproductive Biology
WOS类目	Developmental Biology ; Obstetrics & Gynecology ; Reproductive Biology
WOS记录号	WOS:000819034700003
出版者	OXFORD UNIV PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/203434
专题	生命科学与技术学院_PI研究组_周智组
通讯作者	Zhou, Zhi; Zhang, Feng; Li, Zheng; Yao, Chencheng
作者单位	1.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Androl, Ctr Mens Hlth,Sch Med,Urol Med Ctr, Shanghai, Peoples R China 2.Nanjing Med Univ, Dept Urol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China 3.Fudan Univ, Shanghai Inst Biomed & Pharmaceut Technol, Inst Reprod & Dev,Obstet & Gynecol Hosp, State Key Lab Genet Engn,NHC Key Lab Reprod Regul, Shanghai, Peoples R China 4.Shanghai Key Lab Female Reprod Endocrine Related, Shanghai, Peoples R China 5.Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Ctr Reprod Med, Shanghai, Peoples R China 6.Shanghai Key Lab Assisted Reprod & Reprod Genet, Shanghai, Peoples R China 7.Shanghai Tech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 200135, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yang, Chao,Lin, Xiaoqi,Ji, Zhiyong,et al. Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia[J]. MOLECULAR HUMAN REPRODUCTION,2022,28(7).
APA	Yang, Chao.,Lin, Xiaoqi.,Ji, Zhiyong.,Huang, Yuhua.,Zhang, Ling.,...&Yao, Chencheng.(2022).Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia.MOLECULAR HUMAN REPRODUCTION,28(7).
MLA	Yang, Chao,et al."Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia".MOLECULAR HUMAN REPRODUCTION 28.7(2022).