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Novel mutations in ZP1 and ZP2 cause primary infertility due to empty follicle syndrome and abnormal zona pellucida

  • Genetics
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Abstract

Purpose

Mutations in the zona pellucida glycoprotein genes have been reported to be associated with empty follicle syndrome (EFS) and abnormal zona pellucida (ZP). In this study, we performed genetic analysis in the patients with female infertility due to abnormal zona pellucida and empty follicle syndrome to identify the disease-causing gene mutations in these patients.

Methods

We characterized three patients from two independent families who had suffered from empty follicle syndrome or abnormal zona pellucida. Whole exome sequencing and Sanger sequencing were used to identify the mutations in the families. Western blot was used to check the expression of wild type and mutant disease genes.

Results

We identified two novel mutations in these patients, including a novel compound heterozygous mutation (c.507delC, p. His170fs; c.239 G>A, p. Cys80Tyr and c.241 T>C, p. Tyr81His) in ZP1 gene and a compound mutation in ZP2 gene (c.860_861delTG, p.Val287fs and c.1924 C>T, p.Arg642Ter). Expression of the mutant ZP1 protein (p. Cys80Tyr and p. Tyr81His) is significantly decreased compared with the wild-type ZP1. Other three mutations produce truncated proteins.

Conclusions

Our findings expand the mutational spectrum of ZP1 and ZP2 genes associated with EFS and abnormal oocytes and provide new support for the genetic diagnosis of female infertility.

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Acknowledgments

We would like to thank Sang Qing and Lei Wang from Fudan University for providing the gift of ZP1 and ZP2 plasmids. We also thank all patients for their participation.

Funding

This work was supported by the National Natural Science Foundation of China (81000079, 81170165, and 81870959 to X.Z.) and supported by the Program for HUST Academic Frontier Youth Team.

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Author notes

  1. Geng Luo and Lixia Zhu contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China

    Geng Luo, Zhenxing Liu, Xue Yang & Xianqin Zhang

  2. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Lixia Zhu, Qingsong Xi, Zhou Li & Lei Jin

  3. Reproductive Medical Center, No.924 Hospital of Chinese People’s Liberation Army, Guilin, Guangxi, China

    Jinliang Duan

Authors
  1. Geng Luo
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  2. Lixia Zhu
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  3. Zhenxing Liu
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  4. Xue Yang
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  5. Qingsong Xi
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  6. Zhou Li
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  7. Jinliang Duan
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  8. Lei Jin
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  9. Xianqin Zhang
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Corresponding authors

Correspondence to Lei Jin or Xianqin Zhang.

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Luo, G., Zhu, L., Liu, Z. et al. Novel mutations in ZP1 and ZP2 cause primary infertility due to empty follicle syndrome and abnormal zona pellucida. J Assist Reprod Genet 37, 2853–2860 (2020). https://doi.org/10.1007/s10815-020-01926-z

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