ArticleMolecular genetics & genomic medicine2020
Rare deleterious variants of NOTCH1, GATA4, SMAD6, and ROBO4 are enriched in BAV with early onset complications but not in BAV with heritable thoracic aortic disease.
Article in Molecular genetics & genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Contribution of NOTCH1 genetic variants to bicuspid aortic valve and other congenital lesions.Heart (British Cardiac Society) · 2022Pooled it
- Bicuspid Aortic Valve Disease-Associated Aortopathy in Pediatric Subjects-From Traditional Assessment to Current Advances and Future Perspectives: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Bicuspid Aortic Valve in Heritable Thoracic Aortic Disease: Insights from the Montalcino Aortic Consortium.medRxiv : the preprint server for health sciences · 2025Article
- Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications.American journal of human genetics · 2024Article
- Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes.medRxiv : the preprint server for health sciences · 2024Article
- Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.medRxiv : the preprint server for health sciences · 2024Article
- Valvulopathies and Genetics: Where are We?Reviews in cardiovascular medicine · 2024Review
- Rare genomic copy number variants implicate new candidate genes for bicuspid aortic valve.PloS one · 2024Article
- Novel pathogenic GATA6 variant associated with congenital heart disease, diabetes mellitus and necrotizing enterocolitis.Pediatric research · 2024Article
- Bicuspid Aortic Valve and Thoracic Aortic Disease: Further Evidence of Clinically Silent but Deadly Risk to Family Members of Affected Individuals.Circulation · 2023Article
- Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD.Journal of translational medicine · 2023Article
- Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.Frontiers in cardiovascular medicine · 2023Review
- Association of TGF-β Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections.Frontiers in pharmacology · 2022Review
- Genetic and Developmental Contributors to Aortic Stenosis.Circulation research · 2021Review
- Rare deleterious variants of NOTCH1, GATA4, SMAD6, and ROBO4 are enriched in BAV with early onset complications but not in BAV with heritable thoracic aortic disease.Molecular genetics & genomic medicine · 2020Article
- New Concepts in the Development and Malformation of the Arterial Valves.Journal of cardiovascular development and disease · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBicuspid aortic valve (BAV) is the most common cardiovascular malformation in adults, with a prevalence of 0.5%-2%. The prevalence of BAV in cohorts who were ascertained due to thoracic aortic aneurysms or acute aortic dissections (TAD) is as high as 20%. However, the contribution of causal BAV genes to TAD is not known. Therefore, we evaluated rare deleterious variants of GATA4, NOTCH1, SMAD6, or ROBO4 in patients with BAV who presented with TAD.
methodsOur cohort consisted of 487 probands with Heritable Thoracic Aortic Aneurysms or Dissections (HTAD, 12% BAV, 29% female) and 63 probands with Early onset complications of Bicuspid Aortic Valve disease (EBAV, 63% TAD, 34% female). After whole exome sequencing, we functionally annotated GATA4, NOTCH1, SMAD6, and ROBO4 variants and compared the prevalence of rare variants in these genes to controls without HTAD.
resultsWe identified 11 rare deleterious variants of GATA4, SMAD6, or ROBO4 in 12 (18%) EBAV cases. The burden of rare SMAD6 and GATA4 variants was significantly enriched in EBAV but not in HTAD cases, even among HTAD cases with BAV (p < .003).
conclusionRare variants of NOTCH1, ROBO4, SMAD6, or GATA4 do not significantly contribute to BAV in cohorts with HTAD. We conclude that BAV patients who present with HTAD are a genetically distinct subgroup with implications for genetic testing and prognosis.
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