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