A5086691515- Connective tissue disorders research
- Aortic Disease and Treatment Approaches
- Aortic aneurysm repair treatments
- Congenital heart defects research
- Congenital Heart Disease Studies
- Cardiac Valve Diseases and Treatments
- Cardiomyopathy and Myosin Studies
- Peptidase Inhibition and Analysis
- Pediatric Hepatobiliary Diseases and Treatments
- Williams Syndrome Research
- Genomics and Rare Diseases
- Nuclear Structure and Function
- Heart Failure Treatment and Management
- Congenital limb and hand anomalies
- Protease and Inhibitor Mechanisms
- Cardiac Fibrosis and Remodeling
- Cardiovascular and Diving-Related Complications
- Genetic factors in colorectal cancer
- Microbial metabolism and enzyme function
- Coronary Artery Anomalies
- Macrophage Migration Inhibitory Factor
- Digestive system and related health
- Cardiovascular Function and Risk Factors
- Medical Imaging and Pathology Studies
- Dermatological and Skeletal Disorders
Antwerp University Hospital
2015-2025
University of Antwerp
2015-2025
Radboud University Nijmegen
2021-2024
Radboud University Medical Center
2021-2024
University Medical Center
2024
Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequences of Multiple lines evidence currently suggest that genetic determinants contribute to pathogenesis both and in affected individuals. Despite high heritability, only very few genes have been linked BAV/TAA, such NOTCH1, SMAD6 MAT2A. Moreover, they explain...
Importance Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart malformation. BAV has a heritable component, yet only few causative genes have been identified; understanding genetics key point in developing personalized medicine. Objective To identify new gene for nsBAV. Design, Setting, and Participants This was comprehensive, multicenter, genetic association study based on candidate prioritization familial cohort followed by rare studies replication cohorts....
Background Individuals harbouring SMAD3 pathogenic variants are at risk for aneurysms/dissections throughout the arterial tree. Based on prior reports of sex differences in thoracic aortic aneurysm/dissection, we investigated sexual dimorphism vascular events SMAD3- variant-harbouring patients. Methods We analysed two large pedigrees comprising 84 individuals segregating missense affecting same p.Arg287 residue . excluded individuals<40 years without involvement, as they were too young to...
Background SMAD6 encodes an intracellular inhibitor of the bone morphogenetic protein (BMP) signalling pathway. Until now, rare heterozygous loss-of-function variants in were demonstrated to increase risk disparate clinical disorders including cardiovascular disease, craniosynostosis and radioulnar synostosis. Only two unrelated patients harbouring biallelic presenting a complex phenotype facial dysmorphism have been described. Cases Here, we present first with homozygous variants. The male...
Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity mortality. Loss-of-function variants in LOX, encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to familial TAAD. Using next-generation TAAD gene panel, we identified five additional probands carrying LOX variants, including two missense affecting highly conserved amino acids catalytic domain three truncating variants. Connective tissue manifestations are apparent...
Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent dissection. Angiotensin II receptor blockers (ARBs) prevent formation MFS mouse models. In patients, ARBs only slow down dilation. Downstream signalling from the angiotensin type 1 (AT1R) is mediated by G proteins and β-arrestin recruitment. AT1R also interacts monocyte chemoattractant protein-1 (MCP-1) receptor, resulting inflammation. this study, we explore...
Pathogenic variants in JAG1 are known to cause Alagille syndrome (ALGS), a disorder that primarily affects the liver, lung, kidney, and skeleton. Whereas cardiac symptoms also frequently observed ALGS, thoracic aortic aneurysms have only been reported sporadically postmortem autopsies. We here report two families with segregating present isolated aneurysmal disease, as well first histological evaluation of aneurysm tissue variant carrier. Our observations shed more light on pathomechanisms...
Background:TGFB3 variants cause Loeys-Dietz syndrome type 5, a syndromic form of thoracic aortic aneurysm and dissection. The exact disease phenotype is hard to delineate because few identified cases highly variable clinical representation. Methodology: We provide the results haplotype analysis medical record review features 27 individuals from 5 different families, originating Campine region in Flanders, carrying NM_003239.5(TGFB3):c.787G>C p.(Asp263His) likely pathogenic variant,...
Cardiogeneticsbank@UZA is an academic hospital integrated biobank that collects aortic tissue, blood, cell lines (fibroblasts, vascular smooth muscle cells, peripheral blood mononuclear cells and induced pluripotent stem cells) DNA from patients with cardiogenetic disorders, for both diagnostic research purposes. We adhere to a quality management system have established standard protocols the sampling processing of all patient related materials. embedded in Biobanking Biomolecular Resources...
Objective: Bicuspid aortic valve (BAV) is the most common congenital heart malformation (>1%). Patients with BAV are at risk to develop complications, some life threatening. Previous studies have linked mutations in NOTCH1, SMAD6 and GATA4 trait. However, majority of genetics remains obscure. In this study, we aimed identify genes associated BAV. Methods: Genetic analysis combining familial exome sequencing 69 cases non-syndromic from 28 pedigrees Israeli French origin, targeted resequencing...