Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene

European Journal of Human Genetics : EJHG
Ilse LuyckxMibava Leducq Consortium

Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1-2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution f...Continue Reading

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Citations

Feb 16, 2021·Frontiers in Cell and Developmental Biology·Yuwen ChenYing Liu
Jan 31, 2021·Genes·Tyler J CreamerElena Gallo MacFarlane
Jul 7, 2021·European Heart Journal. Quality of Care & Clinical Outcomes·Idit TesslerDan Gilon
Dec 4, 2021·Aorta : Official Journal of the Aortic Institute at Yale-New Haven Hospital·Idit TesslerRonen Durst

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Methods Mentioned

BETA
dissections
Hi-C
genotyping
PCR

Software Mentioned

DECIPHER
QuantiSNPv1
CNV
MAQ
SIFT
CADD
- Webstore
Polyphen2
gnomAD
ClinVar

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