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Analysis of complex chromosomal rearrangement involving chromosome 6 via the integration of optical genomic mapping and molecular cytogenetic methodologies

Journal of Human Genetics volume 69, pages 3–11 (2024)Cite this article

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Abstract

Complex chromosomal rearrangements (CCRs) can result in spontaneous abortions, infertility, and malformations in newborns. In this study, we explored a familial CCR involving chromosome 6 by combining optical genomic mapping (OGM) and molecular cytogenetic methodologies. Within this family, the father and the paternal grandfather were both asymptomatic carriers of an identical balanced CCR, while the two offspring with an unbalanced paternal-origin CCR and two microdeletions presented with clinical manifestation. The first affected child, a 5-year-old boy, exhibited neurodevelopmental delay, while the second, a fetus, presented with hydrops fetalis. SNP-genotype analysis revealed a recombination event during gamete formation in the father that may have contributed to the deletion in his offspring. Meanwhile, the couple’s haplotypes will facilitate the selection of normal gametes in the setting of assisted reproduction. Our study demonstrated the potential of OGM in identifying CCRs and its ability to work with current methodologies to refine precise breakpoints and construct accurate haplotypes for couples with a CCR.

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Data availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors appreciate the individuals and their families for their participation in this study.

Funding

The research received funding support from the National Key R&D Program of China (2021YFC1005300, 2021YFC1005301) and National High Level Hospital Clinical Research (2022-PUMCH-B-076).

Author information

Author notes

  1. These authors contributed equally: Na Hao, Haijuan Lou.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Na Hao, Mengmeng Li, Hanzhe Zhang, Jiazhen Chang, Qingwei Qi, Xiya Zhou & Yulin Jiang

  2. Becreative Lab Co., Ltd, Beijing, China

    Haijuan Lou, Junjie Bai & Jiangshan Guo

  3. Ecobono (Beijing) Biotech Co., Ltd, Beijing, China

    Yaru Wang

  4. Peking Jabrehoo Med Tech Co., Ltd, Beijing, China

    Yanli Zhang

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  1. Na Hao
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Contributions

Conceptualization, N.H. and Y.J.; methodology, N.H. and Y.J.; software, H.L., M.L. and H.Z.; validation, M.L., H.Z., J.B., Y.W. and Y.Z.; formal analysis, N.H.; writing-original draft preparation, H.L.; writing-review and editing, N.H., J.C., Q.Q., X.Z. and Y.J.; supervision, N.H. and Y.J.; project administration, N.H. and Y.J.; funding acquisition, Y.J. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yulin Jiang.

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The authors declare no competing interests.

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Peking Union Medical College Hospital (HS-2979). All study participants consented to undergo genetic evaluations and signed written informed consent.

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Hao, N., Lou, H., Li, M. et al. Analysis of complex chromosomal rearrangement involving chromosome 6 via the integration of optical genomic mapping and molecular cytogenetic methodologies. J Hum Genet 69, 3–11 (2024). https://doi.org/10.1038/s10038-023-01197-3

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