A novel mutation in ZP3 causes empty follicle syndrome and abnormal zona pellucida formation
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GENETICS
A novel mutation in ZP3 causes empty follicle syndrome and abnormal zona pellucida formation Dazhi Zhang 1 & Lixia Zhu 2 & Zhenxing Liu 1 & Xinling Ren 2 & Xue Yang 1 & Dan Li 2 & Yalin Luo 1 & Xuejie Peng 1 & Xiaopei Zhou 1 & Weimin Jia 1 & Meiqi Hou 1 & Zhou Li 2 & Lei Jin 2 & Xianqin Zhang 1 Received: 19 March 2020 / Accepted: 26 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose To identify disease-causing genes involved in female infertility. Methods Whole-exome sequencing and Sanger DNA sequencing were used to identify the mutations in disease-causing genes. We performed subcellular protein localization, western immunoblotting analysis, and co-immunoprecipitation analysis to evaluate the effects of the mutation. Results We investigated 17 families with female infertility. Whole-exome and Sanger DNA sequencing were used to characterize the disease gene in the patients, and we identified a novel heterozygous mutation (p.Ser173Cys, c.518C > G) in the ZP3 gene in a patient with empty follicle syndrome. When we performed co-immunoprecipitation analysis, we found that the S173C mutation affected interactions between ZP3 and ZP2. Conclusions We identified a novel mutation in the ZP3 gene in a Chinese family with female infertility. Our findings thus expand the mutational and phenotypical spectrum of the ZP3 gene, and they will be helpful in precisely diagnosing this aspect of female infertility. Keywords Female infertility . Empty follicle syndrome (EFS) . Zona pellucida (ZP) . Mutation
Introduction In mammals (including humans), the zona pellucida (ZP) is an extracellular glycoprotein coat that surrounds the oocyte [1], and is vital for oocyte development [2] and the protection of early embryos prior to implantation [3]. During fertilization, Dazhi Zhang and Lixia Zhu contributed equally to this work. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10815-02001995-0. * Zhou Li [email protected] * Xianqin Zhang [email protected] 1
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan 430074, China
2
Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
the ZP plays a critical role in sperm recognition, induction of the acrosome reaction, and prevention of polyspermy [4]. Mammalian ZP glycoproteins contain an N-terminal signal peptide, a ZP domain, a C-terminal peptide with a consensus furin cleavage site (CFCS), and a transmembrane domain (TMD) [1]. ZP glycoproteins are synthesized in the oocyte, and the proteins are secreted extracellularly after the Cterminal CFCS is cleaved by proprotein convertase. The mature ZP glycoproteins are then assembled into a fiber network [5]. There are three types of ZP glycoproteins (ZP1, ZP2, and ZP3) in mice and four types (
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