Trial reportEuropean journal of human genetics : EJHG2019
Confirmation of the role of pathogenic SMAD6 variants in bicuspid aortic valve-related aortopathy.
Trial report in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- 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
- Smad3 deficiency attenuates disease severity in a zebrafish model for Smad6-related aortic disease.Angiogenesis · 2026Article
- Diagnostic Yield of Exome Sequencing in Patients With Congenital Heart Disease From Southern Africa.Circulation. Genomic and precision medicine · 2026Article
- Targeted Sequencing of Human Aorta Tissue Reveals Undiagnosed Heritable Thoracic Aortic Disease.Interdisciplinary cardiovascular and thoracic surgery · 2026Article
- Article
- Age Differences in Aortic Stenosis.Reviews in cardiovascular medicine · 2025Review
- Pathogenic SMAD6 variants in patients with idiopathic and complex congenital heart disease associated pulmonary arterial hypertension.NPJ genomic medicine · 2025Article
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway.Science China. Life sciences · 2024Article
- HomozygousJournal of medical genetics · 2024Article
- 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2024Review
- Valvulopathies and Genetics: Where are We?Reviews in cardiovascular medicine · 2024Review
- Single-Molecule Spatial Transcriptomics of Human Thoracic Aortic Aneurysms Uncovers Calcification-RelatedArteriosclerosis, thrombosis, and vascular biology · 2023Article
- Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.Circulation · 2023Review
- Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.Frontiers in cardiovascular medicine · 2023Article
- SMAD6-deficiency in human genetic disorders.NPJ genomic medicine · 2022Review
- Soft-Tissue Material Properties and Mechanogenetics during Cardiovascular Development.Journal of cardiovascular development and disease · 2022Review
- Association of TGF-β Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections.Frontiers in pharmacology · 2022Review
- Analysis of 200,000 Exome-Sequenced UK Biobank Subjects Implicates Genes Involved in Increased and Decreased Risk of Hypertension.Pulse (Basel, Switzerland) · 2021Article
- Co-Occurring HeterozygousGenes · 2021Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive dilatation of the thoracic aorta leads to thoracic aortic aneurysm (TAA), which is often asymptomatic but predisposes to lethal aortic dissections and ruptures. TAA is a common complication in patients with bicuspid aortic valve (BAV). Recently, rare loss-of-function SMAD6 variants were shown to contribute significantly to the genetic aetiology of BAV/TAA. Intriguingly, patients with craniosynostosis have also been reported to be explained molecularly by similar loss-of-function SMAD6 variants. While significantly reduced penetrance of craniosynostosis has been reported for the SMAD6 variants as such, near-complete penetrance is reached upon co-occurrence with a common BMP2 SNP risk allele. Here, we report on the results of a SMAD6-variant analysis in 473 unrelated non-syndromic TAA patients, of which the SMAD6-positive individuals were also studied for the presence of the BMP2 risk allele. Although only 14% of the TAA patients also presented BAV, all novel likely pathogenic SMAD6 variants (N = 7) were identified in BAV/TAA individuals, further establishing the role of SMAD6 variants to the aetiology of BAV/TAA and revealing limited contribution to TAA development in patients with a tricuspid aortic valve. Familial segregation studies confirmed reduced penetrance (82%) and variable clinical expressivity, with coarctation of the aorta being a common comorbidity. None of our six BMP2+/SMAD6+ patients presented with craniosynostosis. Hence, the proposed digenic model for craniosynostosis was not supported in the presented BAV/TAA cohort, suggesting that additional factors are at play. Finally, our data provide improved insights into the clinical spectrum of SMAD6-related BAV/TAA and has important implications for molecular diagnostics.
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