IMR Press / CEOG / Volume 50 / Issue 10 / DOI: 10.31083/j.ceog5010215
Open Access Original Research
Prenatal Diagnosis of Complex Copy Number Variants in the Fetus and Associated Cytogenetic Findings in Parents
Wei Wang1,†Jing Wang1,†Ye Shi1Bin Zhang1,*
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1 Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Centre, Nanjing Medical University, 213000 Changzhou, Jiangsu, China
*Correspondence: icespringl@163.com (Bin Zhang)
These authors contributed equally.
Clin. Exp. Obstet. Gynecol. 2023, 50(10), 215; https://doi.org/10.31083/j.ceog5010215
Submitted: 28 June 2023 | Revised: 25 July 2023 | Accepted: 2 August 2023 | Published: 18 October 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Co-occurrence of complex copy number variants (CNVs) is associated with more severe clinical expressivity of known syndromes. Few studies discuss diagnosis and genetic counseling for fetuses identified with multiple CNVs. This cohort study aims to summarize findings of complex copy number variants identified via prenatal diagnosis along with the results of parental studies. Methods: 2746 pregnant women were included and diagnosed by chromosomal microarray analysis (CMA) according to different clinical indications. A total of 12 fetuses were diagnosed with complex CNVs (a fetus identified with two or more CNVs simultaneously). Parental analysis was performed by CMA, G-band karyotype analysis, and whole-genome low-coverage mate-pair sequencing (WGL-MPS) based on the size of the fetal imbalances and method resolution. Results: Fetuses carrying complex CNVs were identified as being 0.4% (12/2746) in our cohort. The parental validation study was performed in 8 of 12 complex CNVs cases with the permission of the patients. The primary results suggested that 62.5% (5 out of 8) of fetuses with complex CNVs were from parental inheritance. In these cases, 4 out of 5 were derived from maternal or paternal balanced translocation carriers. Recurrent spontaneous abortion was found in balanced translocation carrier family. Conclusion: In this study, in 4/8 of the fetuses detected with complex CNVs was inherited from a parental balanced translocation. Given the risk of parental balanced rearrangements when fetal complex CNVs are identified, genetic counseling for future pregnancies may be useful for these families.

Keywords
complex CNVs
prenatal diagnosis
genetic counseling
balanced translocation
parental analysis
Funding
82103853/National Natural Science Foundation Youth Fund
CE20225066/Changzhou science and technology support project (Social development)
2022CZBJ089/Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project
Figures
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