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

A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve

“…In the current investigation, the affected family members had also BAV, in addition to ASD, VSD and AF, thus expanding the phenotypic spectrum linked to mutant TBX5. Given that loss-of-function mutations in multiple transcriptional partners of TBX5 (Balistreri et al, 2019), encompassing GATA6 (Gharibeh et al, 2018;Xu et al, 2018), GATA4 (Yang et al, 2017;Li et al, 2018c), GATA5 (Padang et al, 2012;Bonachea et al, 2014;Shi et al, 2014), NKX2-5 (Qu et al, 2014), and TBX20 (Luyckx et al, 2019), have been related to BAV, it is very likely that mutated TBX5 contributes to BAV by reducing expression of the target genes related to BAV morphogenesis in synergy with these partners.…”

Aortic Dissection in an Undiagnosed Familial Form of Bicuspid Aortic Valve with a Short Raphe

“… 3 Gene variants such as SMAD6 , TBX20 , and ROBO4 have recently been identified as genetic factors contributing to this BAV-associated aortopathy. 10 , 11 , 12 However, none of these genes has demonstrated any risk prediction for acute aortic events. Therefore, in the absence of systematic genetic screening, family surveys with transthoracic echocardiography remains the easiest way to identify family cases, which can help to better stratify the risk at the individual level.…”

Bicuspid Aortic Valve: Genetic and Clinical Insights

“… 13 Recently, T-box transcription factor 20 ( TBX20 ) was identified as a possible contributing gene for BAV using copy number variation analysis, explaining 1% of the BAV/TAA cases. 14 This gene was found to be related to SMAD6 in in-vivo studies, and was described in association to other congenital cardiac malformations. 15 Of note, other components of the TGFβ pathway ( TGFβ2 , TGF - β3 , TGF - ßR1 , TGF - ßR2 , and SMAD3 ) are involved in syndromic aortopathies where BAV is present in 5 to 30% of the cases.…”