A5049661907- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Bacterial Genetics and Biotechnology
- Genomics and Rare Diseases
- Congenital heart defects research
- Sports injuries and prevention
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Spaceflight effects on biology
- Cardiac electrophysiology and arrhythmias
- Muscle Physiology and Disorders
- Nuclear Structure and Function
- Skin and Cellular Biology Research
- Neurogenetic and Muscular Disorders Research
- Cardiac Arrhythmias and Treatments
- Congenital Heart Disease Studies
- Cardiac Structural Anomalies and Repair
- Cardiac pacing and defibrillation studies
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Genetics and Physical Performance
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
University Medical Center Groningen
2016-2025
University of Groningen
2016-2025
Amsterdam UMC Location University of Amsterdam
2009-2018
University of Amsterdam
2009-2018
Amsterdam UMC Location Vrije Universiteit Amsterdam
2011-2018
University Medical Center
2011-2018
University Hospital and Clinics
2011-2018
Jordan University of Science and Technology
2018
Vanderbilt University Medical Center
2018
Medisch Centrum Leeuwarden
2018
We sought to determine the influence of genotype on clinical course and arrhythmic outcome among arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated mutation carriers.Pathogenic mutations in desmosomal non-desmosomal genes were identified 577 patients (241 families) from USA Dutch ARVD/C cohorts. Patients with sudden cardiac death (SCD)/ventricular fibrillation (VF) at presentation (n = 36) younger (median 23 vs. 36 years; P < 0.001) than those presenting sustained...
PurposeIntegrating genomic sequencing in clinical care requires standardization of variant interpretation practices. The Clinical Genome Resource has established expert panels to adapt the American College Medical Genetics and Genomics/Association for Molecular Pathology classification framework specific genes diseases. Cardiomyopathy Expert Panel selected MYH7, a key contributor inherited cardiomyopathies, as pilot gene develop broadly applicable approach.MethodsExpert revisions were tested...
Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences genes. However, it cannot yet replace Sanger (SS) in diagnostics because incomplete representation and coverage exons leading to missing clinically relevant mutations. Targeted next-generation (NGS), which a selected fraction genes is sequenced, may circumvent these shortcomings. We aimed determine whether the sensitivity specificity targeted NGS equal those SS. constructed enrichment kit that...
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.Five hundred twenty-eight patients with definite diagnosis no history sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries North America Europe. Over 4.83 (interquartile range 2.44-9.33) years follow-up, 146 (27.7%)...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by arrhythmias and progressive dysfunction. Genetic testing recommended, a pathogenic variant in ARVC-associated gene major criterion for diagnosis according to the 2010 Task Force Criteria. As incorrect attribution of ARVC can contribute misdiagnosis, we assembled international multidisciplinary Clinical Genome Resource Gene Curation Expert Panel reappraise all reported genes.Following comprehensive...
Abstract Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods results Five hundred twenty-eight patients with definite diagnosis no history sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries North America Europe. Over 4.83 (interquartile range 2.44–9.33)...
Anecdotal cases of familial clustering peripartum cardiomyopathy (PPCM) and occurrences PPCM idiopathic dilated (DCM) together have been observed, suggesting that genetic factors play a role in the pathogenesis PPCM. We hypothesized some are part spectrum DCM, presenting period.We reviewed our database 90 DCM families, focusing specifically on presence patients. Then, reverse approach, we 10 patients seen clinic since early 1990s performed cardiological screening first-degree relatives 3 who...
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...
AimPeripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM.
Summary Activity of the Tat machinery for protein transport across inner membrane Escherichia coli and chloroplast thylakoidal requires presence three proteins: TatA, TatB TatC. Here, we show that Gram‐positive bacterium Bacillus subtilis is very different because it contains at least two minimal translocases, each composed one specific TatA TatC component. A third, TatB‐like component apparently not required. This implies proteins B. perform functions both E. thylakoids. Notably,...
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...
BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive testing. A previous retrospective study a research setting showed promising results with diagnoses 57%, but patients were highly selected for known likely Mendelian disorders. The aim of our prospective was assess the speed yield rapid targeted genomic diagnostics application. METHODS: We included 23 children...
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...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients ARVC. However, since this outcome may overestimate the risk for SCD, we aimed specifically life-threatening (LTVA) as a closer surrogate SCD.We assembled retrospective cohort of definite ARVC cases from 15 centers North America Europe. Association 8 prespecified clinical predictors LTVA (SCD,...
The role that mechanical forces play in shaping the structure and function of heart is critical to understanding formation etiology disease but challenging study patients. Engineered tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have potential provide insight into these adaptive maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) afterload (pressure must work against eject blood). Here, we...