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Pathogenic/likely pathogenic copy number variations and regions of homozygosity in fetal central nervous system malformations

  • Maternal-fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations.

Methods

A cohort of 539 fetuses with CNS malformations diagnosed by ultrasound/MRI was retrospectively analyzed between January 2016 and December 2019. All fetuses were analyzed by chromosomal microarray analysis (CMA). Three cases with ROHs detected by CMA were subjected to whole-exome sequencing (WES). The fetuses were divided into two groups according to whether they had other structural abnormalities. The CNS phenotypes of the two groups were further classified as simple (one type) or complicated (≥ 2 types).

Results

(1) A total of 35 cases with P/LP CNVs were found. The incidence of P/LP CNVs was higher in the extra-CNS group [18.00% (9/50)] than in the isolated group [5.32% (26/489)] (P < 0.01), while there was no significant difference between the simpletype and complicated-type groups. (2) In the simple-type group, the three most common P/LP CNV phenotypes were holoprosencephaly, Dandy–Walker syndrome, and exencephaly. There were no P/LP CNVs associated with anencephaly, microcephaly, arachnoid cysts, ependymal cysts, or intracranial hemorrhage. (3) Only four cases with ROHs were found, and there were no cases of uniparental disomy or autosomal diseases.

Conclusion

The P/LP CNV detection rates varied significantly among the different phenotypes of CNS malformations, although simple CNS abnormalities may also be associated with genetic abnormalities.

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Acknowledgements

We thank all the patients who participated in this study.

Funding

This work was supported by the Henan Provincial Health Commission (grant number LHGJ20190361) and by the Key R&D and Promotion Projects in Henan Province (grant number 202102310388).

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Authors and Affiliations

  1. Department of the Third Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China

    Yunxiao Zhi, Ling Liu, Shihong Cui, Ying Li, Xiaolin Chen, Jia Che, Xiao Han & Lanlan Zhao

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  1. Yunxiao Zhi
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  2. Ling Liu
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  3. Shihong Cui
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  4. Ying Li
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  5. Xiaolin Chen
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  8. Lanlan Zhao
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Contributions

YZ, LL and SC: contributed to the conception and design of the study. Material preparation, data collection and analysis were performed by YZ and LL. The critical revision of the manuscript was performed by all authors. All authors commented on the versions of the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Shihong Cui.

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Conflict of interest

All authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Approval was granted by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (date January 27, 2022/No. 2021-165-01).

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Zhi, Y., Liu, L., Cui, S. et al. Pathogenic/likely pathogenic copy number variations and regions of homozygosity in fetal central nervous system malformations. Arch Gynecol Obstet 308, 1723–1735 (2023). https://doi.org/10.1007/s00404-022-06866-w

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