A5016961737- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Cardiac pacing and defibrillation studies
- Prenatal Screening and Diagnostics
- Ion channel regulation and function
- Cystic Fibrosis Research Advances
- Ethics in Clinical Research
- Cardiac Arrhythmias and Treatments
- Congenital Heart Disease Studies
- Fetal and Pediatric Neurological Disorders
- Viral Infections and Immunology Research
- Trypanosoma species research and implications
- Health Systems, Economic Evaluations, Quality of Life
- Congenital heart defects research
- Cardiac Arrest and Resuscitation
- Nuclear Structure and Function
- Williams Syndrome Research
- Autopsy Techniques and Outcomes
- Sports injuries and prevention
- Genomic variations and chromosomal abnormalities
- Connective tissue disorders research
- Skin and Cellular Biology Research
University Medical Center Groningen
2015-2024
University of Groningen
2015-2024
Radboud University Nijmegen
2016-2023
Radboud University Medical Center
2016-2023
John Wiley & Sons (United Kingdom)
2016-2020
Hudson Institute
2019-2020
Amsterdam UMC Location University of Amsterdam
2003-2013
Dialyse Centrum Groningen
2013
Erasmus MC
2010-2012
Amsterdam Public Health
2011
Mutations in SCN5A, the gene encoding cardiac Na(+) channel, have been identified 2 distinct diseases associated with sudden death: one form of long-QT syndrome (LQT(3)) and Brugada syndrome. We screened SCN5A a large 8-generation kindred characterized by high incidence nocturnal death, QT-interval prolongation "Brugada ECG" occurring same subjects. An insertion 3 nucleotides (TGA) at position 5537, predicted to cause an aspartic acid (1795insD) C-terminal domain protein, was linked...
Advances in molecular genetics present new opportunities and challenges for cardiologists who manage patients families with cardiomyopathies. The aims of this position statement the European Society Cardiology Working Group on Myocardial Pericardial Diseases are to review general issues related genetic counselling, family screening testing a cardiomyopathy, provide key messages suggestions clinicians involved their management.
Background— Sudden death mostly follows from cardiac disorders that elicit lethal ventricular arrhythmias. In young individuals, it often remains unexplained because history and/or postmortem analysis are absent or provide no clue. Because such sudden deaths (SUDs) may have heritable causes, cardiological and genetic assessment of surviving relatives SUD victims reveal the underlying disease unmask presymptomatic carriers. We aimed to establish diagnostic yield assessments. Methods Results—...
Background— Mutations in the plakophilin-2 gene ( PKP2 ) have been found patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC). Hence, genetic screening can potentially be a valuable tool diagnostic workup of ARVC. Methods and Results— To establish prevalence character mutations to study potential differences associated phenotype, we evaluated 96 index patients, including 56 who fulfilled published task force criteria. In addition, 114 family members from 34 these...
The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as first-tier test offered to all pregnant women. This started April 1, 2017 the TRIDENT-2 study, licensed by Dutch Ministry of Health. In first year, NIPT was performed in 73,239 pregnancies (42% pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. number trisomies 21 (239, 0.33%), 18 (49, 0.07%), 13 (55, 0.08%) found this is comparable earlier studies,...
Atrial standstill (AS) is a rare arrhythmia that occasionally appears to be genetically determined. This study investigates the genetic background of this arrhythmogenic disorder in large family. Forty-four family members were clinically evaluated. One deceased and three living relatives unambiguously affected by AS. All other appeared unaffected. Candidate gene screening revealed novel mutation cardiac sodium channel SCN5A (D1275N) all five unaffected relatives, relative was an obligate...
Background— Catecholaminergic polymorphic ventricular tachycardia is a disease characterized by arrhythmias elicited exclusively under adrenergic stress. Additional features include baseline bradycardia and, in some patients, right fatty displacement. The clinical spectrum expanded the 2 families described here. Methods and Results— Sixteen members from separate have been clinically evaluated followed over last 15 years. In addition to exercise-related arrhythmias, they showed abnormalities...
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.
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...
Background— Sudden cardiac death is often caused by inherited arrhythmia syndromes, particularly if it occurs at a young age. In 1996, we started cardiogenetics clinic aimed diagnosing such syndromes and providing timely (often presymptomatic) treatment to families in which or sudden existed. We studied the yield of DNA testing for these using candidate-gene approach over our 15 years experience. Methods Results— analyzed testing. subanalyses, differences time, between probands with isolated...
Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with failure and sudden death. Quality of life psychological distress were found to be impaired in HCM patients but have never been assessed mutation carriers, or without manifest HCM. We aimed assess quality distress, using standardized questionnaires, identify sociodemographic, clinical, risk illness perception related predictors thereof 228 carriers. carriers' overall scores did not differ from the Dutch...
Technological advances have increased the availability of genomic data in research and clinic. If, over time, interpretation significance changes, or new information becomes available, question arises as to whether recontacting patient and/or family is indicated. The Public Professional Policy Committee European Society Human Genetics (ESHG), together with groups from UK Netherlands, developed recommendations on which, after public consultation, been endorsed by ESHG Board. In clinical...
We recently identified a novel mutation of SCN5A (1795insD) in large family with features both long QT syndrome type 3 and the Brugada syndrome. The purpose this study was to detail clinical efficacy pacemaker therapy preventing sudden death family.The group consisted 116 adult members: 60 carriers (29 males) 56 noncarriers (28 mutant gene. Investigations included 24-hour Holter monitoring, ergometry, electrophysiologic studies. Mean, lowest, highest heart rate were lower carriers, but...
Previously published diagnostic systems, based on ECG analysis and clinical parameters (Schwartz criteria Keating criteria), have been used to estimate the probability of inherited long QT syndrome (LQTS). Nowadays, a certain diagnosis can often be made by DNA testing. We aimed establish predictive power Schwartz criteria, using testing as reference, determine best strategy.We studied 513 relatives (aged >10 years) 77 consecutive LQTS probands with known disease-causing mutation. The...