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Extended application of PGT-M strategies for small pathogenic CNVs

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

Abstract

Purpose

The preimplantation genetic testing for aneuploidy (PGT-A) platform is not currently available for small copy-number variants (CNVs), especially those < 1 Mb. Through strategies used in PGT for monogenic disease (PGT-M), this study intended to perform PGT for families with small pathogenic CNVs.

Methods

Couples who carried small pathogenic CNVs and underwent PGT at the Reproductive and Genetic Hospital of CITIC-Xiangya (Hunan, China) between November 2019 and April 2023 were included in this study. Haplotype analysis was performed through two platforms (targeted sequencing and whole-genome arrays) to identify the unaffected embryos, which were subjected to transplantation. Prenatal diagnosis using amniotic fluid was performed during 18–20 weeks of pregnancy.

Results

PGT was successfully performed for 20 small CNVs (15 microdeletions and 5 microduplications) in 20 families. These CNVs distributed on chromosomes 1, 2, 6, 7, 13, 15, 16, and X with sizes ranging from 57 to 2120 kb. Three haplotyping-based PGT-M strategies were applied. A total of 89 embryos were identified in 25 PGT cycles for the 20 families. The diagnostic yield was 98.9% (88/89). Nineteen transfers were performed for 17 women, resulting in a 78.9% (15/19) clinical pregnancy rate after each transplantation. Of the nine women who had healthy babies, eight accepted prenatal diagnosis and the results showed no related pathogenic CNVs.

Conclusion

Our results show that the extended haplotyping-based PGT-M strategy application for small pathogenic CNVs compensated for the insufficient resolution of PGT-A. These three PGT-M strategies could be applied to couples with small pathogenic CNVs.

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Data availability

The targeted sequencing or SNP array data in this study have not been deposited in public repository because of privacy and ethical restrictions but are available from the corresponding author on request.

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Acknowledgements

We thank all the involved families for participating in and supporting this study.

Funding

This work was supported by the National Key Research and Developmental Program of China (2022YFC2702604 to Y.-Q.T.), the National Natural Science Foundation of China (81971447 and 82171608 to Y.-Q.T.,), the Hunan Provincial Natural Science Foundation of China (2023JJ40459 to W.L.W., 2022JJ30772 to Ju.D.), China Postdoctoral Science Foundation (2022M721124 to W.L.W.), and Research Grant from Reproductive and Genetic Hospital of CITIC-Xiangya (YNXM-202305 to W.L.W., YNXM-202002 to Ju.D.).

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Author notes

  1. X.H. and W.L.W. contributed equally to this work.

Authors and Affiliations

  1. Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410008, China

    Xiao Hu, Weili Wang, Keli Luo, Jing Dai, Yi Zhang, Zhenxing Wan, Wenbin He, Shuoping Zhang, Lanlin Yang, Qin Tan, Wen Li, Qianjun Zhang, Fei Gong, Guangxiu Lu, Yue-Qiu Tan, Ge Lin & Juan Du

  2. Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410078, China

    Weili Wang, Wenbin He, Qianjun Zhang, Yue-Qiu Tan & Ge Lin

  3. College of Life Science, Hunan Normal University, Changsha, 410081, China

    Wenbin He, Wen Li, Qianjun Zhang, Fei Gong, Yue-Qiu Tan, Ge Lin & Juan Du

  4. Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, 410000, China

    Wen Li, Qianjun Zhang, Fei Gong, Guangxiu Lu, Yue-Qiu Tan, Ge Lin & Juan Du

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  1. Xiao Hu
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Contributions

Conceptualization: Ju.D., G.L., G.X.L., Y.-Q.T.; investigation: X.H., W.L.W., Ji.D.; funding acquisition: Ju.D., Y.-Q.T., W.L.W.; methodology: X.H., Y.Z., W.B.H.; clinical resources: F.G., K.L.L., S.P.Z., L.L.Y; project administration and supervision: G.L., Y.-Q.T., Q.J.Z., W.L.; validation: Ji.D., Z.X.W., Y.Z., Q.T.; writing—original draft: W.L.W., X.H.; writing—review and editing: Ju.D., G.L.

Corresponding authors

Correspondence to Ge Lin or Juan Du.

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The authors declare no competing interests.

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G.L. and Ju.D. cosupervised the study and should be considered shared last authors.

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Hu, X., Wang, W., Luo, K. et al. Extended application of PGT-M strategies for small pathogenic CNVs. J Assist Reprod Genet 41, 739–750 (2024). https://doi.org/10.1007/s10815-024-03028-6

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