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

Authors :
Meerschaut I
Vergult S
Dheedene A
Menten B
De Groote K
De Wilde H
Muiño Mosquera L
Panzer J
Vandekerckhove K
Coucke PJ
De Wolf D
Callewaert B
Source :
Genes [Genes (Basel)] 2021 Jul 08; Vol. 12 (7). Date of Electronic Publication: 2021 Jul 08.
Publication Year :
2021

Abstract

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.

Details

Language :
English
ISSN :
2073-4425
Volume :
12
Issue :
7
Database :
MEDLINE
Journal :
Genes
Publication Type :
Academic Journal
Accession number :
34356064
Full Text :
https://doi.org/10.3390/genes12071048