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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00078053" target="_blank" >RIV/00023001:_____/19:00078053 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/19:10395122 RIV/00064203:_____/19:10395122

Result on the web

<a href="https://www.nature.com/articles/s41431-019-0364-y" target="_blank" >https://www.nature.com/articles/s41431-019-0364-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41431-019-0364-y" target="_blank" >10.1038/s41431-019-0364-y</a>

Result language

angličtina

Original language name

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

Original language description

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 for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European journal of human genetics

ISSN

1018-4813

e-ISSN

—

Volume of the periodical

27

Issue of the periodical within the volume

7

Country of publishing house

AT - AUSTRIA

Number of pages

11

Pages from-to

1033-1043

UT code for WoS article

000471871000005

EID of the result in the Scopus database

2-s2.0-85062338955