Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia

doi:10.1186/s12958-022-00900-x

	Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia
	Li, Peng 1; Ji, Zhiyong 1,2; Zhi, Erlei 1; Zhang, Yuxiang 1; Han, Sha 1; Zhao, Liangyu 1; Tian, Ruhui 1; Chen, Huixing 1; Huang, Yuhua 1; Zhang, Jing 3; Chen, Huirong 1; Zhao, Fujun 1; Zhou, Zhi4 ; Li, Zheng 1; Yao, Chencheng 1,4
	2022-01-28
发表期刊	REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY (IF:4.2[JCR-2023],5.3[5-Year])
EISSN	1477-7827
卷号	20 期号:1
发表状态	已发表
DOI	10.1186/s12958-022-00900-x
摘要	Background Non-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive. Methods Four Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA. Results We identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM_002440.4: c.805_812del: p.V269Qfs15) and one patient with NOA (P21504) in another Chinese family (NM_002440.4: c.2220_2223del:p.K741Rfs2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM_002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs11), and the patient with NOA (P9540) (NM_002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers. Conclusions We identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA.
关键词	Non-obstructive azoospermia Meiosis MSH4 Male infertility
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[82001530,82171597,81871215,81971368,82171590,31801219,31771650] ; Clinical Research Innovation Plan of Shanghai General Hospital["KD007-ly01","CTCCR-2019D07"] ; Clinical Research Plan of SHDC[SHDC-2020CR3077B] ; Key Project of Research and Development of Ningxia Hui Autonomous Region of China[2020BFH02002] ; Shanghai Science and Technology Innovation Action Plan Project[20Y11907600] ; Shanghai Sailing Program["20YF1439500","20YF1453700"]
WOS研究方向	Endocrinology & Metabolism ; Reproductive Biology
WOS类目	Endocrinology & Metabolism ; Reproductive Biology
WOS记录号	WOS:000749204400001
出版者	BMC
Scopus 记录号	2-s2.0-85123816537
来源库	Scopus
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/154101
专题	生命科学与技术学院_PI研究组_周智组
通讯作者	Zhou, Zhi; Li, Zheng; Yao, Chencheng
作者单位	1.Department of Andrology,Center for Men’s Health,Department of ART,Institute of Urology,Urologic Medical Center,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200080,China 2.State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Nanjing,211116,China 3.The Reproductive Medicine Research Center,The Sixth Affiliated Hospital of Sun Yat-sen University,Guangzhou,510620,China 4.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,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	Li, Peng,Ji, Zhiyong,Zhi, Erlei,et al. Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia[J]. REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY,2022,20(1).
APA	Li, Peng.,Ji, Zhiyong.,Zhi, Erlei.,Zhang, Yuxiang.,Han, Sha.,...&Yao, Chencheng.(2022).Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia.REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY,20(1).
MLA	Li, Peng,et al."Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia".REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY 20.1(2022).