A5051807425- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Genomics and Rare Diseases
- Cardiac pacing and defibrillation studies
- Sports injuries and prevention
- Congenital heart defects research
- Viral Infections and Immunology Research
- Cardiovascular Function and Risk Factors
- Amyloidosis: Diagnosis, Treatment, Outcomes
- RNA modifications and cancer
- Genetics and Physical Performance
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Congenital Heart Disease Studies
- Neurogenetic and Muscular Disorders Research
- Medical Imaging and Pathology Studies
- Parathyroid Disorders and Treatments
- Mitochondrial Function and Pathology
- Cardiac Arrhythmias and Treatments
- Genomic variations and chromosomal abnormalities
- Cerebrovascular and genetic disorders
- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
University Medical Center Groningen
2016-2025
University of Groningen
2015-2024
University Medical Center
2011-2018
Academic Medical Center
2011-2018
Amsterdam UMC Location VUmc
2011-2018
University Hospital and Clinics
2011-2018
Jordan University of Science and Technology
2018
Vanderbilt University Medical Center
2018
Medisch Centrum Leeuwarden
2018
Radboud University Nijmegen
2018
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited disease with incomplete penetrance and variable expression. Causative mutations in genes encoding 5 desmosomal proteins are found ≈50% of ARVD/C index patients. Previous genotype-phenotype relation studies involved mainly overt patients, so follow-up data on relatives scarce.One hundred forty-nine patients (111 male patients; age, 49±13 years) according to 2010 Task Force criteria 302 from...
The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies is associated with an increased risk of malignant arrhythmias end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, factors for in cohort carriers.Using the family tree mortality ratio method 403 carriers, we found standardized 1.7 (95% confidence interval, 1.4-2.0) significant excess starting from age 25 years. Cardiological...
Abstract The diagnostic yield of exome and genome sequencing remains low (8–70%), due to incomplete knowledge on the genes that cause disease. To improve this, we use RNA-seq data from 31,499 samples predict which specific disease phenotypes, develop GeneNetwork Assisted Diagnostic Optimization (GADO). We show this unbiased method, does not rely upon individual genes, is effective in both identifying previously unknown gene associations, flagging have been incorrectly implicated GADO can be...
We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid valve, coarctation aorta, hypoplastic left syndrome.NOTCH1 was screened for 428 nonsyndromic probands with LS-CHD, family histories were obtained all. When mutation detected, relatives also tested.In 148/428 patients (35%), familial. Fourteen (3%; 5 RNA splicing mutations, 8 truncating 1 whole-gene deletion) 11...
This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed is compared an existing PLN model.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a hereditary cardiomyopathy characterized by fibrofatty replacement of cardiomyocytes, tachyarrhythmias and sudden death. ARVD/C mainly caused mutations in genes encoding desmosomal proteins. However, the pathogenicity variants not always clear. Therefore, we created an online database (www.arvcdatabase.info), providing information on ARVD/C-associated genes. We searched literature using its underlying as search terms....
Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by myocardial atrophy, fibro-fatty replacement, and a high risk of ventricular arrhythmias that lead to sudden death. In 2009, genetic data from 57 publications were collected in the arrhythmogenic right dysplasia/cardiomyopathy (ARVD/C) Genetic Variants Database (freeware available at http://www.arvcdatabase.info), which comprised 481 variants eight ACM-associated genes. recent years, deep sequencing has...
Recently, we showed that the c.40_42delAGA (p.Arg14del) mutation in phospholamban (PLN) gene can be identified 10-15 % of Dutch patients with dilated cardiomyopathy or arrhythmogenic cardiomyopathy. The burden p.Arg14del was illustrated by high rate appropriate ICD discharges and a positive family history for sudden cardiac death.Our goal to evaluate geographical distribution origin this specific Netherlands get an estimation prevalence population cohort. Therefore, investigated postal codes...
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with pathogenic/likely pathogenic (P/LP) variants in genes encoding the cardiac desmosomal proteins. Origin of these variants, including de novo mutation rate and extent founder versus recurrent has implications for variant adjudication clinical care, yet this never been systematically investigated. Methods: We identified arrhythmogenic probands who met 2010 Task Force Criteria had undergone genotyping that...
Phospholamban (PLN) plays a role in cardiomyocyte calcium handling as primary inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The p.(Arg14del) pathogenic variant the PLN gene results high risk developing dilated or arrhythmogenic cardiomyopathy with heart failure. There is no established treatment other than standard failure therapy transplantation. In this study, we generated novel mouse model PLN-R14del variant, performed detailed phenotyping, and tested efficacy therapies...
Stringent variant interpretation guidelines can lead to high rates of variants uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada (BrS). Quantitative disease-specific customization American College Medical Genetics Genomics/Association Molecular Pathology (ACMG/AMP) address this false negative rate.We compared rare frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) 3335 BrS (SCN5A) cases the International LQTS/BrS Consortia...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic condition caused predominantly by mutations within desmosomal genes. The mutation leading to ARVC-5 was recently identified on the island of Newfoundland and fully penetrant missense p.S358L in TMEM43. Although TMEM43-p.S358L carriers were also found USA, Germany, Denmark, relationship between North American European patients disease mechanism this remained be clarified. We screened 22 unrelated ARVC without genes...
The p.Arg14del founder mutation in the gene encoding phospholamban (PLN) is associated with an increased risk of malignant ventricular arrhythmia (VA) and heart failure. It has been shown to lead calcium overload, cardiomyocyte damage, eventually myocardial fibrosis. This study sought investigate function, extent localization fibrosis associations ECG features VA PLN carriers.Cardiovascular magnetic resonance (CMR) data 150 carriers were analysed retrospectively. Left (LV) right (RV)...
Abstract Recent advancements in next generation sequencing (NGS) technology have led to the identification of giant sarcomere gene, titin ( TTN ), as a major human disease gene. Truncating variants (TTNtv) especially A-band region account for 20% dilated cardiomyopathy (DCM) cases. Much attention has been focused on assessment and interpretation TTNtv disease; however, missense non-frameshifting insertions/deletions (NFS-INDELs) are difficult assess interpret clinical diagnostic workflow....
Objective To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients TTR variant (TTRv) carriers.
Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions.To create a large national ACM cohort with vast amount of uniformly collected high-quality data that readily available for future research.This multicentre, longitudinal, observational includes (1) patients definite diagnosis, (2) at-risk relatives patients, (3) ACM-associated mutation carriers. At baseline every follow-up visit,...
Neuromuscular disorders (NMDs) are clinically and genetically heterogeneous. Accurate molecular genetic diagnosis can improve clinical management, provides appropriate counseling testing of relatives, allows potential therapeutic trials.To establish the utility panel-based whole exome sequencing (WES) in NMDs a population with children adults various neuromuscular symptoms.Clinical sequencing, followed by diagnostic interpretation variants genes associated NMDs, was performed cohort 396...