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. 2019 Jun;7(6):e658.
doi: 10.1002/mgg3.658. Epub 2019 Apr 19.

The frequency of CNVs in a cohort population of consecutive fetuses with congenital anomalies after the termination of pregnancy

Gorazd Rudolf  1 , Luca Lovrečić  1 , Nataša Tul  2 , Nataša Teran  1 , Borut Peterlin  1
Affiliations

The frequency of CNVs in a cohort population of consecutive fetuses with congenital anomalies after the termination of pregnancy

Gorazd Rudolf et al. Mol Genet Genomic Med. 2019 Jun.

Abstract

Background: The implementation of molecular karyotyping has resulted in an improved diagnostic yield in the genetic diagnostics of congenital anomalies, detected prenatally or after the termination of pregnancy. However, the systematic epidemiologic ascertainment of copy number variations in the etiology of congenital anomalies has not yet been sufficiently explored.

Methods: Consecutive fetuses, altogether 204, with major single or multiple congenital anomalies were ascertained by using the SLOCAT registry for the period from 2011 to 2015. After excluding aneuploidies by using conventional karyotyping or Quantitative Fluorescence-Polymerase Chain Reaction, array comparative genomic hybridization was performed for the detection of copy number variations.

Results: We identified pathogenic or likely pathogenic copy number variations in 14 fetuses (6.8%); 2.9% in fetuses with isolated, and 3.9% in fetuses with multiple congenital anomalies. Additionally, aneuploidies and major structural chromosomal abnormalities were detected in 40.2%.

Conclusion: Our systematic approach of ascertaining congenital anomalies resulted in explaining the etiology of congenital anomalies in 47% of fetuses after the termination of pregnancy. By using array comparative genomic hybridization, we found that copy number variations represent an important part in the etiology of multiple, as well as isolated congenital anomalies, which indicates the importance of analyzing copy number variations in the diagnostic approach of fetuses with congenital anomalies after the termination of pregnancy.

Keywords: congenital anomalies; copy number variations; epidemiology; molecular karyotyping; termination of pregnancy.

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Conflict of interest statement

This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors. The authors stated that there are no conflicts of interest regarding the publication of this manuscript. The authors also state that they have had full control of all primary data and that they agree to allow the Journal to review their data if requested.

Figures

Figure 1
Figure 1
Representation of single CAs, according to the ICD10 nomenclature, in the study sample. CAs—congenital anomalies
See this image and copyright information in PMC

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