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The mutation-free embryo for in vitro fertilization selected by MALBAC-PGD resulted in a healthy live birth from a family carrying PKD 1 mutation

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

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD, autosomal dominant PKD or adult-onset PKD) is the most prevalent and potentially lethal kidney disease that is hereditary and lacks effective treatment. Preimplantation genetic diagnosis (PGD) of embryos in assistant reproductive technology (ART) helps to select mutation-free embryos for blocking ADPKD inheritance from the parents to their offspring. However, there are multiple pseudogenes in the PKD1 coding region, which make blocking ADPKD inheritance by PGD complicated and difficult. Therefore, this technique has not been recommended and used routinely to ADPKD family plan.

Methods and Results

Here, we report a new strategy of performing PGD in screening (target-) mutation-free embryos. We firstly used a long-range PCR amplification and next generation sequencing to identify the potential PKD1 mutant(s). After pathogenic variants were detected, multiple annealing and looping-based amplification cycles (MALBAC), a recently developed whole genome amplification method, was used to screen embryo cells. We successfully distinguished the mutated allele among pseudogenes and obtained mutation-free embryos for implantation. The first embryo transfer attempt resulted in a healthy live birth free of ADPKD condition and chromosomal anomalies which was confirmed by aminocentesis at week 18 of gestation, and by performing live birth genetic screening.

Conclusions

The first MALBAC-PGD attempt in ADPKD patient resulted in a healthy live birth free of ADPKD and chromosomal anomalies. MALBAC-PGD also enables selecting embryos without aneuploidy together and target gene mutation, thereby increasing implantation and live birth rates.

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Acknowledgements

This work was supported by funds from the National Natural Science Foundation of China (31371172, 81670612 to CM), Shanghai Top Priority Key Clinical Disciplines Construction Project (to CM), The National Key Research and Development Program of China (No. 2016YFC0901502), and Systemic Redesign and Demonstration for Early Detection, Evaluation and Management of Chronic Kidney Disease in Shanghai (SCREEMING Study GWIV-18 to CM).

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Author notes

  1. Wen Li and Yiyi Ma contributed equally to this work.

Authors and Affiliations

  1. Reproductive center, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China

    Wen Li, Ningxia Sun & Liang Wang

  2. Division of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China

    Yiyi Ma, Shengqiang Yu, Dongping Chen, Bo Yang & Changlin Mei

  3. Beijing San Valley Biotechnology Inc., Beijing, 100000, People’s Republic of China

    Guijiang Yang & Yangyang Li

  4. Department of Clinical Research, Yikon Genomics Co. Ltd., Shanghai, 201499, People’s Republic of China

    Sijia Lu

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  1. Wen Li
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  11. Changlin Mei
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Correspondence to Changlin Mei.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

The study protocol and all subjects who participated in this study were approved by the Institutional Review Board of our institute in which informed consent was obtained from all families prior to participation in accordance with institutional and national guidelines.

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Li, W., Ma, Y., Yu, S. et al. The mutation-free embryo for in vitro fertilization selected by MALBAC-PGD resulted in a healthy live birth from a family carrying PKD 1 mutation. J Assist Reprod Genet 34, 1653–1658 (2017). https://doi.org/10.1007/s10815-017-1018-z

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  • DOI: https://doi.org/10.1007/s10815-017-1018-z

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