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

Identifikátory výsledku

  • Kód výsledku v 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>

  • Nalezeny alternativní kódy

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

  • Výsledek na webu

    <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>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

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

  • Popis výsledku v původním jazyce

    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.

  • Název v anglickém jazyce

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

  • Popis výsledku anglicky

    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.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30201 - Cardiac and Cardiovascular systems

Návaznosti výsledku

  • Projekt

  • Návaznosti

    N - Vyzkumna aktivita podporovana z neverejnych zdroju

Ostatní

  • Rok uplatnění

    2019

  • Kód důvěrnosti údajů

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

Údaje specifické pro druh výsledku

  • Název periodika

    European journal of human genetics

  • ISSN

    1018-4813

  • e-ISSN

  • Svazek periodika

    27

  • Číslo periodika v rámci svazku

    7

  • Stát vydavatele periodika

    AT - Rakouská republika

  • Počet stran výsledku

    11

  • Strana od-do

    1033-1043

  • Kód UT WoS článku

    000471871000005

  • EID výsledku v databázi Scopus

    2-s2.0-85062338955