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A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

We aimed to identify pathogenic variants in a female patient with primary infertility and recurrent failure of in vitro fertilization with zygotic cleavage failure.

Methods

The genomic DNA from the affected individual was subjected to whole-exome sequencing and the variant was confirmed by Sanger sequencing. The functional effect of the identified variant was further investigated in 293 T cells.

Results

We identified a novel homozygous deletion in BTG4 (c.580_616del) in the affected individual. The deletion results in frameshift and replacement of the last 29 residues (aa195-223) with 66 random amino acids. The mutated amino acid residues are highly conserved among mammalian species. Co-immunoprecipitation in 293 T cells showed that the mutation abolished the interaction between BTG4 and PABPN1L.

Conclusion

This study conforms previous studies and expands the mutational spectrum of BTG4. Our findings prove the functional importance of the C-terminal of BTG4. BTG4 is a potential diagnostic and therapeutic target for patients suffering from zygotic cleavage failure.

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Data availability

The data that support the fndings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

We would like to sincerely thank the patient and her family for their support and participation.

Funding

This work was supported by the National Natural Science Foundation of China (grant 31970559 to BJ), the Key Research and Development Program of Shandong Province (grant 2016GSF201143 to BJ), and the Young Scholars Program of Shandong University (to BJ).

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Authors and Affiliations

  1. The Key Laboratory of Experimental Teratology of the Ministry of Education and Department of Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China

    Yufeng Wang, Qingtao Qin, Yuting Liu, Molin Wang, Yongxin Zou, Yaoqin Gong & Baichun Jiang

  2. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China

    Yang Yang, Shan Dong & Haibin Zhou

Authors
  1. Yufeng Wang
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  2. Qingtao Qin
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  3. Yang Yang
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  4. Shan Dong
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  5. Yuting Liu
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  6. Molin Wang
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  7. Yongxin Zou
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  8. Yaoqin Gong
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  9. Haibin Zhou
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  10. Baichun Jiang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Baichun Jiang, Haibin Zhou, and Yufeng Wang. The first draft of the manuscript was written by Baichun Jiang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Haibin Zhou or Baichun Jiang.

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Ethics approval and consent to participate

We obtained informed consent from the patient and her family members. The study was approved by the Ethics Committee of Center for Reproductive Medicine, Qilu Hospital, Shandong University.

Conflict of interest

The authors declare no competing interests.

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Wang, Y., Qin, Q., Yang, Y. et al. A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility. J Assist Reprod Genet 40, 75–81 (2023). https://doi.org/10.1007/s10815-022-02664-0

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  • DOI: https://doi.org/10.1007/s10815-022-02664-0

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