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New biallelic mutations in PADI6 cause recurrent preimplantation embryonic arrest characterized by direct cleavage

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

Abstract

Purpose

To investigate the pathogenesis of the recurrent preimplantation embryonic arrest characterized by direct cleavage.

Methods

Two affected individuals underwent time-lapse imaging to observe the cleavage behaviors in their final ICSI attempts. In addition, both patients were subjected to whole-exome sequencing. After the identification of possible causative genes, molecular modeling analyses were used to evaluate the possible effects of candidate mutations on protein secondary structure.

Results

All the bipronucleated (2PN) zygotes from both individuals presented multiple abnormal cleavage behaviors, particularly direct cleavage (DC) and subsequent cleavage arrest. Mutation analysis identified one new frameshift mutation c.1521dupC (p.S508Qfs*5) and two missense mutations c.A1117C and c.C1708T (p.T373P and p.R570C, respectively) of the PADI6 gene, which were in the protein-arginine deiminase (PAD) domain and highly conserved.

Conclusion

This study expands the mutation spectrum of PADI6 and is the first to propose that the preimplantation embryonic arrest with concomitant abnormal cleavage behaviors, especially DC, maybe associated with PADI6 mutations.

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Acknowledgments

We thank all families that participated in our study.

Funding

This study is supported by grants from National Key R&D Program of China (grant 2018YFC1003100, to L.H.) and Natural Science Foundation of Hunan Province (2018JJ3893).

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Authors and Affiliations

  1. Reproductive and Genetic Hospital of Citic-Xiangya, ChangSha, 410078, China

    Wei Zheng, Can Dai, Jing Guo, Changfu Lu, Fei Gong, Guangxiu Lu & Ge Lin

  2. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, ChangSha, 410078, China

    Longbin Chen, Jing Dai, Changfu Lu, Fei Gong, Guangxiu Lu & Ge Lin

  3. Laboratory of Reproductive and Stem Cell Engineering, National Health and Family Planning Commission, ChangSha, 410078, China

    Longbin Chen, Jing Dai, Changfu Lu, Fei Gong, Guangxiu Lu & Ge Lin

Authors
  1. Wei Zheng
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  2. Longbin Chen
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  3. Jing Dai
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  4. Can Dai
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  5. Jing Guo
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  6. Changfu Lu
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  7. Fei Gong
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  8. Guangxiu Lu
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  9. Ge Lin
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Corresponding author

Correspondence to Ge Lin.

Ethics declarations

This study was approved by the Ethics Committee of the Reproductive and Genetic Hospital of CITIC-Xiangya (reference LL-SC-2017-009).

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The authors declare that they have no conflicts of interest.

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Zheng, W., Chen, L., Dai, J. et al. New biallelic mutations in PADI6 cause recurrent preimplantation embryonic arrest characterized by direct cleavage. J Assist Reprod Genet 37, 205–212 (2020). https://doi.org/10.1007/s10815-019-01606-7

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  • DOI: https://doi.org/10.1007/s10815-019-01606-7

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