Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays

Huili Xue,Xuemei Chen,Hailong Huang,Na Lin,Min Lin,Liangpu Xu,Yan Wang,Aili Yu

doi:10.1038/s41598-021-83147-7

Huili Xue, Xuemei Chen + Show 6 more

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https://doi.org/10.1038/s41598-021-83147-7

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Journal: Scientific Reports	Publication Date: Mar 5, 2021
Citations: 11	License type: open-access

Affiliation: Fujian Medical University

Abstract

Etiopathogenesis of fetal ventriculomegaly is poorly understood. Associations between fetal isolated ventriculomegaly and copy number variations (CNVs) have been previously described. We investigated the correlations between fetal ventriculomegaly—with or without other ultrasound anomalies—and chromosome abnormalities. 222 fetuses were divided into four groups: (I) 103 (46.4%) cases with isolated ventriculomegaly, (II) 41 (18.5%) cases accompanied by soft markers, (III) 33 (14.9%) cases complicated with central nervous system (CNS) anomalies, and (IV) 45 (20.3%) cases with accompanying anomalies. Karyotyping and single nucleotide polymorphism (SNP) array were used in parallel. Karyotype abnormalities were identified in 15/222 (6.8%) cases. Karyotype abnormalities in group I, II, III, and IV were 4/103 (3.9%), 2/41 (4.9%), 4/33 (12.1%), and 5/45 (11.1%), respectively. Concerning the SNP array analysis results, 31/222 (14.0%) were CNVs, CNVs in groups I, II, III, and IV were 11/103 (10.7%), 6/41 (14.6%), 9/33 (27.3%), and 5/45 fetuses (11.1%), respectively. Detections of clinical significant CNVs were higher in non-isolated ventriculomegaly than in isolated ventriculomegaly (16.81% vs 10.7%, P = 0.19). SNP arrays can effectively identify CNVs in fetuses with ventriculomegaly and increase the abnormal chromosomal detection rate by approximately 7.2%, especially ventriculomegaly accompanied by CNS anomalies.

Highlights

Fetal lateral ventricle width is a common test parameter in prenatal ultrasound screening
Parents of 12 fetuses were genotyped by Single nucleotide polymorphism (SNP) array to determine the origin of the copy number variations (CNVs)
Among the fetuses with pathogenic/likely pathogenic CNVs, parental testing was carried out in five; two occurred de novo, and three cases were inherited from normal parents

Summary

Introduction

Fetal lateral ventricle width is a common test parameter in prenatal ultrasound screening. Fetal VM is one of the most common indicators of central nervous system (CNS) abnormalities in prenatal ultrasound screening. VM is a nonspecific soft marker of prenatal ultrasound screening and is the most common hallmark of fetal CNS abnormalities. Routine karyotype analysis is a common method for detecting chromosomal abnormalities and plays an important role in the diagnosis of fetal VM. Chromosomal microarray analysis has improved the detection rate of CNVs that cannot be diagnosed using karyotyping. CNVs have been reported in approximately 6% of fetuses with ultrasound anomalies (UAs) and a normal karyotype[6]. We retrospectively analyzed the prenatal diagnosis results of these 222 fetuses and clarified the association between fetal VM with or without other UAs and chromosomal abnormalities

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Conclusion