| http://purl.uniprot.org/citations/30796334 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30796334 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30796334 | http://www.w3.org/2000/01/rdf-schema#comment | "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 (Nā=ā7) 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."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41431-019-0363-z"xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41431-019-0363-z"xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Hoischen A."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Hoischen A."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Dietz H."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Dietz H."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Loeys B."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Loeys B."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Boeckx N."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Boeckx N."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Kempers M."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Kempers M."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Vandeweyer G."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Vandeweyer G."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Luyckx I."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Luyckx I."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Van Laer L."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Van Laer L."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Verstraeten A."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Verstraeten A."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Timmermans J."xsd:string |
| http://purl.uniprot.org/citations/30796334 | http://purl.uniprot.org/core/author | "Timmermans J."xsd:string |