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A comprehensive PGT-M strategy for ADPKD patients with de novo PKD1 mutations using affected embryo or gametes as proband

  • Genetics
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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the development of renal cysts and progression to renal failure. Preimplantation genetic testing-monogenic disease (PGT-M) is an alternative option to obtain healthy babies. However, de novo PKD1 mutation of one of the spouses or the absence of a positive family history poses a serious challenge to PGT-M. Here, we described a comprehensive strategy which includes preimplantation genetic testing for aneuploidies (PGT-A) study and monogenic diagnosis study for ADPKD patients bearing de novo mutations. The innovation of our strategy is to use the gamete (polar body or single sperm) as proband for single-nucleotide polymorphism (SNP) linkage analysis to detect an embryo’s carrier status. Nine ADPKD couples with either de novo mutation or without a positive family history were recruited and a total of 34 embryos from 13 PGT-M cycles were examined. Within these nine couples, two successfully delivered healthy babies had their genetic status confirmed by amniocentesis. This study provides a creative approach for embryo diagnosis of patients with de novo mutations or patients who lack essential family members for linkage analysis.

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Data availability

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

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Acknowledgements

We thank all the staffs in the Center for Reproductive Medicine of Peking University Third hospital, for supporting all the procedures of IVF-PGT.

Funding

This project is funded by Beijing Municipal Science and Technology Commission (Z191100006619073, Z191100006619075).

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Authors and Affiliations

  1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49, North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China

    Yuqian Wang, Fan Zhai, Shuo Guan, Zhiqiang Yan, Xiaohui Zhu, Ying Kuo, Nan Wang, Xu Zhi, Ying Lian, Jin Huang, Jialin Jia, Ping Liu, Rong Li, Jie Qiao & Liying Yan

  2. National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, 100191, China

    Yuqian Wang, Fan Zhai, Shuo Guan, Zhiqiang Yan, Xiaohui Zhu, Ying Kuo, Nan Wang, Xu Zhi, Ying Lian, Jin Huang, Jialin Jia, Ping Liu, Rong Li, Jie Qiao & Liying Yan

  3. Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China

    Yuqian Wang, Fan Zhai, Shuo Guan, Zhiqiang Yan, Xiaohui Zhu, Ying Kuo, Nan Wang, Xu Zhi, Ying Lian, Jin Huang, Jialin Jia, Ping Liu, Rong Li, Jie Qiao & Liying Yan

  4. Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China

    Yuqian Wang, Fan Zhai, Shuo Guan, Zhiqiang Yan, Xiaohui Zhu, Ying Kuo, Nan Wang, Xu Zhi, Ying Lian, Jin Huang, Jialin Jia, Ping Liu, Rong Li, Jie Qiao & Liying Yan

  5. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100191, China

    Yuqian Wang & Jie Qiao

  6. Beijing Advanced Innovation Center for Genomics, Beijing, 100191, China

    Jie Qiao

Authors
  1. Yuqian Wang
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  2. Fan Zhai
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  3. Shuo Guan
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  4. Zhiqiang Yan
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  5. Xiaohui Zhu
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  7. Nan Wang
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  8. Xu Zhi
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  9. Ying Lian
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  10. Jin Huang
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  11. Jialin Jia
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  12. Ping Liu
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  13. Rong Li
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  14. Jie Qiao
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  15. Liying Yan
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Corresponding author

Correspondence to Liying Yan.

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The authors declare no competing interests.

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Yuqian Wang and Fan Zhai are joint First Authors and contributed equally to this work.

Supplementary information

Supplemental Fig. 1

Pedigree charts for the nine cases. Filled symbols represent patient affected with ADPKD; open symbols represent wild-type individuals with respect to ADPKD. Circles and squares indicate females and males, respectively. Couples indicated by asterisks asked for PGT-M treatment. (PNG 208 kb)

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Wang, Y., Zhai, F., Guan, S. et al. A comprehensive PGT-M strategy for ADPKD patients with de novo PKD1 mutations using affected embryo or gametes as proband. J Assist Reprod Genet 38, 2425–2434 (2021). https://doi.org/10.1007/s10815-021-02188-z

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  • DOI: https://doi.org/10.1007/s10815-021-02188-z

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