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Chromosomal Copy Number Variation Analysis in Pregnancy Products from Recurrent and Sporadic Miscarriage Using Next-Generation Sequencing

  • Genetics: Original Article
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Abstract

Chromosomal abnormality is one of the causes of fetal miscarriage. The potential differences of fetal chromosomal abnormalities in sporadic miscarriage (SM) and recurrent miscarriage (RM) remain unclear. The purpose of this study was to investigate copy number variations (CNVs) in SM and RM to provide useful genetic guidance for pregnancy and prenatal diagnosis. Four hundred eight samples of aborted fetuses were analyzed by CNV sequencing, and further functional enrichment analysis was performed. Chromosomal abnormalities were identified in 218 (53.4%) fetuses. There were 62 cases (15.2%) with structural chromosomal abnormalities, including 41 with VUS CNVs, 8 with pathogenic CNVs (pCNVs), and 5 with likely pCNVs. Duplications or deletions of 7p22, 8p22, 8p23, and Xp22.31 were significantly more common in RM cases and therefore believed to be related to RM. A total of 289 genes were identified, and 29 different functions were enriched as potential RM candidate genes and functions, which were mainly concentrated in 4 functional categories: chemokines and chemotaxis, protease activity and protein modification, defense response to bacterial and fungal infections, and immune response. The results of this study may improve our understanding of the etiology of RM and contribute to the establishment of a population-based genetic marker information for RM.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

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Acknowledgements

The author would like to thank other colleagues who were not listed in the authorship of Department of Laboratory Medicine, Center for Precision Medicine and Center for Prenatal Diagnosis, Meizhou People’s Hospital (Huangtang Hospital), for their helpful comments on the manuscript.

Funding

This study was supported by the Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population under Grant 2018B030322003; the Science and Technology Program of Meizhou under Grant 2019B0202001; and the Key Scientific and Technological Project of Meizhou People’s Hospital under Grant MPHKSTP-20190102.

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Author notes

  1. Xia Zhang and Heming Wu equally contributed to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China

    Xia Zhang

  2. Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China

    Xia Zhang, Heming Wu, Zhonghang Gu, Zhikang Yu, Liubing Lan & Qingyan Huang

  3. Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China

    Heming Wu, Zhikang Yu & Qingyan Huang

  4. Department of Plastic Surgery, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, China

    Zhonghang Gu

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  1. Xia Zhang
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Corresponding author

Correspondence to Qingyan Huang.

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Ethics Approval

This study was conducted on the basis of the Declaration of Helsinki and was supported by the Ethics Committee of the Meizhou People’s Hospital.

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Each patient provided informed written consent, and the hospital’s ethics committees approved enrollment in the study.

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Each participant had signed the consent form for the use of her personal data for research use and publication.

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The authors declare no competing interests.

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Cite this article

Zhang, X., Wu, H., Gu, Z. et al. Chromosomal Copy Number Variation Analysis in Pregnancy Products from Recurrent and Sporadic Miscarriage Using Next-Generation Sequencing. Reprod. Sci. 29, 2927–2936 (2022). https://doi.org/10.1007/s43032-022-00969-0

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  • DOI: https://doi.org/10.1007/s43032-022-00969-0

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