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. 2024 Feb 18;17(1):4.
doi: 10.1186/s13039-024-00671-7.

Identification of chromosomal abnormalities in miscarriages by CNV-Seq

Yuqi Shao #  1   2   3 , Saisai Yang #  1   2   3 , Lin Cheng  1   2   3 , Jie Duan  1   2   3 , Jin Li  2   4 , Jiawei Kang  1   2   3 , Fang Wang  1   2   3 , Juan Liu  1   2   3 , Fang Zheng  2   4 , Jianhong Ma  1   2   3 , Yuanzhen Zhang  5   6   7
Affiliations

Identification of chromosomal abnormalities in miscarriages by CNV-Seq

Yuqi Shao et al. Mol Cytogenet. .

Abstract

Objective: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies.

Methods: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs).

Results: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein-protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages.

Conclusion: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

Keywords: CNV-Seq; Chromosomal abnormalities; Copy number variants; Miscarriage.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Distribution of chromosomal abnormalities. (A) General classification of variants with respective proportions. (B) The number of aneuploid and P CNVs in different chromosomes. (C) Distribution of cases with positive or negative chromosomal results in various maternal age groups. (D) The bar plot showed the distribution of early or late miscarriage in various maternal age groups and the line chart showed the trends of chromosomal abnormalities detected in different gestational weeks as the maternal age increased
Fig. 3
Fig. 3
GO, KEGG analysis and PPI network of selected genes. (A and B) GO analysis of 226 genes (P < 0.05). (C) Eleven enriched pathways in KEGG analysis (P < 0.05). (D) TP53, CTNNB1, UBE3A, EP300, SOX2 and ATM were selected to be significant genes in PPI network
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References

    1. Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, Brosens JJ, Brewin J, Ramhorst R, Lucas ES, McCoy RC, Anderson R, Daher S, Regan L, Al-Memar M, Bourne T, MacIntyre DA, Rai R, Christiansen OB, Sugiura-Ogasawara M, Odendaal J, Devall AJ, Bennett PR, Petrou S, Coomarasamy A. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021;397:1658–1667. doi: 10.1016/S0140-6736(21)00682-6. - DOI - PubMed
    1. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601–611. doi: 10.1016/S0140-6736(06)69204-0. - DOI - PubMed
    1. Pylyp LY, Spynenko LO, Verhoglyad NV, Mishenko AO, Mykytenko DO, Zukin VD. Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases. J Assist Reprod Genet. 2018;35(2):265–271. doi: 10.1007/s10815-017-1069-1. - DOI - PMC - PubMed
    1. Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Med. 2013;11:154. doi: 10.1186/1741-7015-11-154. - DOI - PMC - PubMed
    1. Bagheri H, Mercier E, Qiao Y, Stephenson MD, Rajcan-Separovic E. Genomic characteristics of miscarriage copy number variants. Mol Hum Reprod. 2015;21(8):655–661. doi: 10.1093/molehr/gav030. - DOI - PMC - PubMed