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Preimplantation genetic testing for inborn errors of metabolism: observations from a reproductive genetic laboratory in China

Journal of Human Genetics volume 70, pages 113–119 (2025)Cite this article

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Abstract

In this study, we aimed to apply preimplantation genetic testing for monogenic disorders (PGT-M) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) to block the transmission of inborn errors of metabolism (IEMs). After the disease-causing variants were identified through genetic testing, four carrier couples having children affected with IEMs, including methylmalonic aciduria, glutaric acidemia type 1, beta-ketothiolase deficiency, and ornithine transcarbamylase deficiency, sought PGT-M. A series of PGT procedures involving intracytoplasmic sperm injection, blastocyst culture, biopsy of trophectoderm cells, and next-generation sequencing (NGS)-based MARSALA, was performed to provide comprehensive chromosome screening and variant gene analysis. Finally, embryos were selected for transfer, and prenatal diagnosis was conducted to confirm the PGT-M results. All four carrier couples obtained transferrable embryos after PGT. The results of the prenatal diagnosis were consistent with the PGT results, and all couples gave birth to healthy babies free of IEMs. The results of this study confirm that NGS-based MARSALA is an effective approach for families with IEMs to prevent the subsequent transmission of pathological genetic variants to the next generation.

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Acknowledgements

We are grateful to the families for their participation in the study. Furthermore, we especially thank the staff at Fujun Genetic Biotechnology Co., Ltd. and Yikon Genomics Co., Ltd.

Funding

This work was supported by the Natural Science Foundation of Fujian Province, China [No. 2023J011341] to Zhihong Wang.

Author information

Author notes

  1. These authors contributed equally: Xiaoli Li, Qiuxiang Huang, Fuchun Zhong.

Authors and Affiliations

  1. Department of Clinical Laboratory Medicine, Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, Fujian, China

    Xiaoli Li

  2. Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, Fujian, China

    Qiuxiang Huang, Yun Liu & Zhibiao Chen

  3. Laboratory of Basic Medicine, Fujian Provincial Key Laboratory of Transplant Biology, Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, Fujian, China

    Fuchun Zhong, Juan Lin, Zhongli Fan, Fenghua Lan & Zhihong Wang

Authors
  1. Xiaoli Li
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  2. Qiuxiang Huang
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  3. Fuchun Zhong
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  4. Yun Liu
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  6. Juan Lin
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  7. Zhongli Fan
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  8. Fenghua Lan
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  9. Zhihong Wang
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Contributions

Xiaoli Li, Qiuxiang Huang, and Fuchun Zhong conceived and designed the study. Xiaoli Li, Qiuxiang Huang, Fuchun Zhong, Zhibiao Chen, Juan Lin, and Zhongli Fan conducted and performed the experiments. Yun Liu, Fenghua Lan, and Zhihong Wang contributed to the genetic counseling. Xiaoli Li, Qiuxiang Huang, Fuchun Zhong, and Zhihong Wang are responsible for data collection and analysis. Xiaoli Li and Qiuxiang Huang wrote the manuscript. Zhihong Wang received funding support and supervised the study. All authors read and approved the manuscript.

Corresponding author

Correspondence to Zhihong Wang.

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Competing interests

The authors declare no competing interests.

Ethics approval

The protocols for this study were evaluated and approved by the Ethics Committee of Fuzhou General Hospital (Ethics approval no. 2013027).

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Li, X., Huang, Q., Zhong, F. et al. Preimplantation genetic testing for inborn errors of metabolism: observations from a reproductive genetic laboratory in China. J Hum Genet 70, 113–119 (2025). https://doi.org/10.1038/s10038-024-01307-9

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