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Blocker displacement amplification-based genetic diagnosis for autosomal dominant polycystic kidney disease and the clinical outcomes of preimplantation genetic testing

  • Genetics
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Abstract

Objective

Given that the molecular diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is complicated, we aim to apply blocker displacement amplification (BDA) on the mutational screening of PKD1 and PKD2.

Methods

A total of 35 unrelated families with ADPKD were recruited from the Center for Reproductive Medicine, Women and Children’s Hospital of Chongqing Medical University (Chongqing, China), from October 2018 to October 2021. Long-range PCR followed by next-generation sequencing were applied for resequencing of PKD1 and PKD2, and the putatively disease-causative variants were verified with BDA. The effects of ADPKD on male and female infertility and the factors influencing the clinical outcomes of preimplantation genetic testing (PGT) for ADPKD were investigated.

Results

A total of 26 PKD1 variants and 5 PKD2 variants were identified, of which 13 were newly discovered. The BDA system worked effectively for eliminating the interference of pseudogenes in genetic testing of PKD1 (1–33 exons) with different concentrations of genome DNA. The females with ADPKD have no specific infertility factors, while 68.2% of the affected men were with abnormal sperm concentration and/or motility with an indefinite genotype–phenotype relationship. As for PGT, the fertilization rate of couples with the male partner having ADPKD was relatively lower compared to those with the female partner being affected. The ADPKD patients receiving PGT usually achieved high rates of live births.

Conclusion

These findings expanded the variant spectrum of PKD genes and emphasized the application prospect of blocker displacement amplification on PKD1-related genetic diagnosis.

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Data availability

All data generated or analyzed during this study are included in the article and the supplementary information files.

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Funding

This study was supported by grants from the Natural Science Foundation of Chongqing (CSTC2021JCYJ-MSXMX0722) and the Chongqing Health Center for Women and Children (2020YJMS01).

Author information

Authors and Affiliations

  1. Center for Reproductive Medicine, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China

    Tingting Lin, Haibing Yu, Qi Zhang, Ke Chen, Yezhou Xiang, Dongyun Liu & Guoning Huang

  2. Chongqing Health Center for Women and Children, Chongqing, China

    Tingting Lin, Haibing Yu, Qi Zhang, Ke Chen, Yezhou Xiang, Dongyun Liu & Guoning Huang

  3. Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China

    Tingting Lin, Qi Zhang & Guoning Huang

  4. NuProbe China, Shanghai, China

    Junfeng Luo & Bohao Dong

  5. AmCare Genomics Lab, Guangzhou, China

    Wei Zhang

Authors
  1. Tingting Lin
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  2. Junfeng Luo
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  3. Haibing Yu
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  4. Bohao Dong
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  5. Qi Zhang
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  6. Wei Zhang
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  7. Ke Chen
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  8. Yezhou Xiang
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  9. Dongyun Liu
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  10. Guoning Huang
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Contributions

T.T Lin, J.F Luo, D.Y Liu, and G.N Huang conceived and designed the study. B.H Dong, W Zhang, and K Chen carried out the experiments. H.B Yu and Y.Z Xiang provided the clinical samples. D.Y Liu conducted the PGT cycle. T.T Lin wrote the manuscript. D.Y Liu and G.N Huang critically commented on and edited the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Dongyun Liu or Guoning Huang.

Ethics declarations

Ethics statement

The studies involving human participants were reviewed and approved by the Clinical Application and Ethics Committee of Human Assisted Reproductive Technology of Chongqing Health Center for Women and Children.

Consent

Informed consent was obtained from the proband/participants.

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The authors declare no competing interests.

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Lin, T., Luo, J., Yu, H. et al. Blocker displacement amplification-based genetic diagnosis for autosomal dominant polycystic kidney disease and the clinical outcomes of preimplantation genetic testing. J Assist Reprod Genet 40, 783–792 (2023). https://doi.org/10.1007/s10815-023-02722-1

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  • DOI: https://doi.org/10.1007/s10815-023-02722-1

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