# The Genetic and Imaging Key to Understanding Bicuspid Aortic Valve Disease
## 2 Genetic Components of BAV
### Other Relevant Genes
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Category** & **Authors** & **Number of Participants** & **Study Design** & **Sequencing Technology** & **Main Findings** \\ \hline  & & & & & Identified a novel loss of function mutation (p.Tyr291) in NOTCH1 \\  & [22] & 4 family members & & Targeted Sequencing & associated with BAV, ventricular septal defect, thoracic aortic aneurysm, and aortic stenosis. \\ \hline GATA & [23] & 40 BAV patients, 40 controls & Prospective Cohort Study & Targeted Sequencing & Rare variants of the GATA5 gene, highly expressed in the endocardium, linked to non-syrdromic BAV. \\ \hline  & & & & Identified a novel heterozygous GATA4 mutation (p.E147X) associated with BAV, with a loss of function disrupting synergistic transcriptional activation with NKX2.5. \\ \hline  & [7] & 150 patients, 300 controls & Case-Control Study & Direct Sequencing & Identified a novel heterozygous GATA4 mutation (p.E147X) associated with BAV, with a loss of function disrupting synergistic transcriptional activation with NKX2.5. \\ \hline  & [24] & 466 BAV cases, 4660 controls & Genome Wide Association Study & Whole Genome Sequencing (WGS) & GATA4 identified as a predisposing gene for BAV, with odds ratios ranging from 1.4 to 2.4 depending on the variant. \\ \hline  & [25] & Family study152 unrelated patients affected with BAV and 200 unrelated healthy controls without BAV & Case-Control Study & Targeted Sequencing & GATA4 identified as a predisposing gene for BAV, with odds ratios ranging from 1.4 to 2.4 depending on the variant. \\ \hline SMAD6 & [10] & Large cohort study & Cohort Study & Targeted resequencing & SMAD6 as an important contributor to BAV-associated thoracic aortic aneurysm. \\ \hline  & & & & Identified a novel SMAD6 variant (c.1168\(\_\)1173 dup; \\  & [11] & Single case report & Case Report & Whole Exome Sequencing (WES) & p.Gly390\(\_\)Ile391 dup) associated with severely calcified BAV and thoracic aortic aneurysm, with impaired inhibition of BMP signaling. \\ \hline  & [27] & Case reports, 22 patients & Case Report & Targeted Sequencing & Recurrent rare missense and loss of function variants in SMAD4 and SMAD6 identified in non-syrdromic grounds with BAV and TAA. \\ \hline  & [27] & Case reports, 22 patients & Case Report & Targeted Sequencing & Recurrent rare missense and loss of function variants in SMAD4 and SMAD6 identified in non-syrdromic grounds with BAV and TAA. \\ \hline  & & & & Identified a novel heterozygous NKX2.5 mutation (p.K192X) associated with BAV, showing no transcriptional activity and disrupted interaction with GATA5. \\ \hline BMP2 & [13] & Case Report & Case Report & Whole Exome Sequencing (WES) & De novo pathogenic BMP2 variant associated with craniofacial dysmorphisms, skeletal abnormalities, BAV, and aortic root aneurysm. \\ \hline  & & & & & \\ \end{tabular}
\end{table} 
Table 1: _Cont._Understanding these genetic determinants provides a foundation for linking molecular mechanisms to imaging findings. Future research combining genetic screening with advanced imaging modalities, such as 4D Flow MRI and high-resolution CMR, could enable predictive models to identify at-risk individuals earlier, improve risk stratification, and guide personalized management strategies for BAV patients.