A Reassessment of Copy Number Variations in Congenital Heart Defects: Picturing the Whole Genome

Ilse Meerschaut, Sarah Vergult, Annelies Dheedene, Björn Menten, Katya De Groote, Hans De Wilde, Laura Muino Mosquera, Joseph Panzer, Kristof Vandekerckhove, Paul J. Coucke, Daniel De Wolf, Bert Callewaert

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences directly or through interference of gene expression. Recent studies in cancer and limb defects pinpointed the relevance of non-coding gene regulatory elements such as long non-coding RNAs (lncRNAs) and topologically associated domain (TAD)-related gene-enhancer interactions. The contribution of such non-coding elements is largely unexplored in congenital heart defects (CHD). We performed a retrospective analysis of CNVs reported in a cohort of 270 CHD patients. We reviewed the diagnostic yield of pathogenic CNVs, and performed a comprehensive reassessment of 138 CNVs of unknown significance (CNV-US), evaluating protein-coding genes, lncRNA genes, and potential interferences with TAD-related gene-enhancer interactions. Fifty-two of the 138 CNV-US may relate to CHD, revealing three candidate CHD regions, 19 candidate CHD genes, 80 lncRNA genes of interest, and six potentially CHD-related TAD interferences. Our study thus indicates a potential relevance of non-coding gene regulatory elements in CNV-related CHD pathogenesis. Shortcomings in our current knowledge on genomic variation call for continuous reporting of CNV-US in international databases, careful patient counseling, and additional functional studies to confirm these preliminary findings.

Original languageEnglish
Article number1048
Number of pages16
Issue number7
Publication statusPublished - Jul 2021

Bibliographical note

Funding Information:
Acknowledgments: This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from https://deciphergenomics. org/about/stats and via email from contact@deciphergenomics.org. Funding for the DECIPHER project was provided by Wellcome.

Funding Information:
Funding: This project was funded by grant G028415N of the Research Foundation Flanders (FWO) to B.C. and P.J.C., Methusalem grant BOFMET2015000401from the Special Research Fund of Ghent University, and starting grant BOF16/STA/045 from the Special Research Fund of Ghent University Hospital to B.C.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright 2022 Elsevier B.V., All rights reserved.


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