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Application of the PGT-M strategy using single sperm and/or affected embryos as probands for linkage analysis in males with hereditary tumor syndromes without family history

Journal of Human Genetics volume 68, pages 813–821 (2023)Cite this article

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Abstract

Hereditary tumor syndromes have garnered substantial attention due to their adverse effects on both the physical and psychological health of patients, as well as the elevated risk of transmission to subsequent generations. This has prompted a growing interest in exploring preimplantation genetic testing (PGT) as a treatment option to mitigate and eliminate these impacts. Several studies have demonstrated that de novo variants have become a great cause of many hereditary tumor syndromes, which introduce certain difficulties to PGT. In the absence of adequate genetic linkage information (parents and offspring), haplotype construction seems unrealizable. In the study, researchers used single sperm or affected embryos as proband to perform single-nucleotide polymorphism linkage analysis for cases with de novo variants. For complicated variants, the strategy that sperm combined with embryo detection will increase accuracy while avoiding the limitations and potential failures of using a single detection material. The study recruited 11 couples with male de novo carriers, including 3 tumor types and 4 genes. To date, 4 couples have been clinically confirmed as pregnant and three healthy babies have been born. The results of amniocentesis or umbilical cord blood verification were consistent with the results of PGT-M. The study aims to introduce the application of the PGT-M strategy in hereditary tumor syndromes.

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Acknowledgements

This work was supported by National Key Research and Development Program (2019YFA0801401).

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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, China

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

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

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

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

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

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

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

  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

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  1. Xi Chen
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by XC and YW. Other authors helped to collect follow-up clinical outcomes. The first draft of the manuscript was written by XC, YW and JQ. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jie Qiao.

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Chen, X., Wang, Y., Guan, S. et al. Application of the PGT-M strategy using single sperm and/or affected embryos as probands for linkage analysis in males with hereditary tumor syndromes without family history. J Hum Genet 68, 813–821 (2023). https://doi.org/10.1038/s10038-023-01188-4

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