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A Novel Homozygous Nonsense Mutation in ZP1 Causes Female Infertility due to Empty Follicle Syndrome

  • Genetics: Original Article
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Abstract

ZP1 is a critical glycoprotein in the formation of the zona pellucida. It plays an indispensable role in the maturation of oocytes. To identify the causative gene of empty follicle syndrome (EFS) in a patient from a consanguineous family, whole-exome sequencing was performed in the proband. We identified a novel homozygous nonsense mutation c.1260C > G (p. Tyr420X) in the ZP1 gene from two primary infertile patients. Western blot showed that Y420X mutation in ZP1 gene produced a truncated protein. However, the mutation had no significant effect on subcellular localization of the mutant protein. Our findings confirmed the important role of the ZP1 gene in human female reproduction, enriched the mutation spectrums of ZP1 gene, and expanded its applications in the clinical and molecular diagnoses of EFS.

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Acknowledgements

We thank all patients for their participation. We would like to thank Prof. Lei Wang from Fudan University for kindly providing the gift of ZP1 plasmid. We also thank the Research Core Facilities for Life Science (HUST).

Funding

This work was supported by grants from the National Natural Science Foundation of China (81000079, 81170165 and 81870959 to X.Z.) and supported by Program for HUST Academic Frontier Youth Team (2016QYTD02).

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Author notes

  1. Tingting Zou and Qingsong Xi 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, 430074, Wuhan, Hubei, China

    Tingting Zou, Zhenxing Liu, Meiqi Hou & Xianqin Zhang

  2. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China

    Qingsong Xi, Zhou Li, Lixia Zhu & Lei Jin

Authors
  1. Tingting Zou
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  2. Qingsong Xi
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  3. Zhenxing Liu
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  4. Zhou Li
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  5. Meiqi Hou
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  6. Lixia Zhu
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  7. Lei Jin
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  8. Xianqin Zhang
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Corresponding authors

Correspondence to Lixia Zhu or Xianqin Zhang.

Ethics declarations

Research Involving Human Participants and/or Animals

Two primary infertility women due to large polar body oocyte, embryonic development, or fertilization disorder from two families were recruited from the Reproductive Medicine Center, Tongji Hospital, Huazhong University of Science and Technology.

Informed Consent

All participants in the study signed informed consent. All studies on human subjects were approved by the Ethics Committee of Huazhong University of Science and Technology.

Conflict of Interest

The authors declare no competing interests.

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Zou, T., Xi, Q., Liu, Z. et al. A Novel Homozygous Nonsense Mutation in ZP1 Causes Female Infertility due to Empty Follicle Syndrome. Reprod. Sci. 29, 3516–3520 (2022). https://doi.org/10.1007/s43032-022-01024-8

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  • DOI: https://doi.org/10.1007/s43032-022-01024-8

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