Publicaties
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Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection Universiteit Antwerpen Vrije Universiteit Brussel
Background Missense variants in SMAD2, encoding a key transcriptional regulator of transforming growth factor beta signalling, were recently reported to cause arterial aneurysmal disease. Objectives The aims of the study were to identify the genetic disease cause in families with aortic/arterial aneurysmal disease and to further define SMAD2 genotypephenotype correlations. Methods and results Using gene panel sequencing, we identified a SMAD2 ...
Aortic aneurysm Universiteit Antwerpen
Confirmation of the role of pathogenic SMAD6 variants in bicuspid aortic valve-related aortopathy Universiteit Antwerpen
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 ...
Molecular characterization and investigation of the role of genetic variation in phenotypic variability and response to treatment in a large pediatric Marfan syndrome cohort Universiteit Antwerpen
PURPOSE In a large cohort of 373 pediatric patients with Marfan syndrome (MFS) with a severe cardiovascular phenotype, we explored the proportion of patients with MFS with a pathogenic FBN1 variant and analyzed whether the type/location of FBN1 variants was associated with specific clinical characteristics and response to treatment. Patients were recruited on the basis of the following criteria: aortic root z-score > 3, age 6 months to 25 ...
Molecular autopsy and subsequent functional analysis reveal de novo DSG2 mutation as cause of sudden death Universiteit Antwerpen
Sudden cardiac death (SCD) is a common cause of death in young adults. In up to 80% of cases a genetic cause is suspected. Next-generation sequencing of candidate genes can reveal the cause of SCD, provide prognostic management, and facilitate pre-symptomatic testing and prevention in relatives. Here we present a proband who experienced SCD in his sleep for which molecular autopsy was performed. We performed a post-mortem genetic analysis of a ...
varAmpliCNV Universiteit Antwerpen
Motivation: Computational identification of copy number variants (CNVs) in sequencing data is a challenging task. Existing CNV-detection methods account for various sources of variation and perform different normalization strategies. However, their applicability and predictions are restricted to specific enrichment protocols. Here, we introduce a novel tool named varAmpliCNV, specifically designed for CNV-detection in amplicon-based targeted ...
Improved selection of zebrafish CRISPR editing by early next-generation sequencing based genotyping Universiteit Antwerpen
Despite numerous prior attempts to improve knock-in (KI) efficiency, the introduction of precise base pair substitutions by the CRISPR-Cas9 technique in zebrafish remains challenging. In our efforts to generate KI zebrafish models of human CACNA1C mutations, we have tested the effect of several CRISPR determinants on KI efficiency across two sites in a single gene and developed a novel method for early selection to ameliorate KI efficiency. We ...
Two novel presentations of KCNMA1-related pathology Universiteit Antwerpen KU Leuven
Background KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations. Methods Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well-known clinical entities. Results In an 8-year-old boy presenting with severe aortic ...
iPSC-cardiomyocyte models of Brugada syndrome Universiteit Antwerpen Universiteit Gent
Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient ...