A5023476503- Cardiac electrophysiology and arrhythmias
- Hemoglobinopathies and Related Disorders
- Genomics and Rare Diseases
- Iron Metabolism and Disorders
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiac Valve Diseases and Treatments
- Cardiac Arrhythmias and Treatments
- Genetics and Neurodevelopmental Disorders
- Cardiac pacing and defibrillation studies
- Cardiac Structural Anomalies and Repair
- Congenital Heart Disease Studies
- Genetic Associations and Epidemiology
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Syndromes and Imprinting
- Congenital heart defects research
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Blood groups and transfusion
- Autophagy in Disease and Therapy
- Cardiovascular Effects of Exercise
- Neurogenetic and Muscular Disorders Research
- ECG Monitoring and Analysis
Leiden University Medical Center
2017-2024
Hospital for Sick Children
2016-2024
Leiden University
2024
University of Amsterdam
2014
Academic Medical Center
2009-2014
University Medical Center Utrecht
2010
Netherlands Heart Institute
2010
University of Szeged
2009
University of Louisville
2009
Hungarian Academy of Sciences
2009
Background— Brugada syndrome, characterized by ST-segment elevation in the right precordial ECG leads and development of life-threatening ventricular arrhythmias, has been associated with mutations 6 different genes. We identify characterize a mutation new gene. Methods Results— A 64-year-old white male displayed type 1 V1 V2 during procainamide challenge. Polymerase chain reaction-based direct sequencing was performed using candidate gene approach. missense (L10P) detected exon SCN3B , β3...
Variants in SCN10A, which encodes a voltage-gated sodium channel, are associated with alterations of cardiac conduction parameters and the rhythm disorder Brugada syndrome; however, it is unclear how SCN10A variants promote dysfunctional conduction. Here we showed by high-resolution 4C-seq analysis Scn10a-Scn5a locus murine heart tissue that enhancer located Scn10a, encompassing functional variant rs6801957, interacts promoter Scn5a, channel–encoding gene critical for We observed SCN5A...
ABSTRACT In the presented case of familial mitral valve prolapse, whole exome sequencing was used to reveal a missense variant in PDLIM7 gene. This gene is considered possible novel candidate for MVP based on knock‐out mice and zebrafish showing abnormalities.
Beta (β) thalassemia is an inherited disorder that occurs following mutations or deletions in the β globin gene. Rarely, it caused by variants genes coding for erythroid transcriptional factors trans-acting factors. Here, we report three novel of SUPT5H revealed next generation sequencing. This, gene has been progressively acknowledged as a mimicker trait two independent individuals and one family. These have same features, including hypochromic microcytic indices, increased Hb A2 levels,...
In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these lie within inter-genic regions. The underlying trait-associated variants likely reside in regulatory regions exert their effect by modulating gene expression. Hence, the key to unraveling molecular mechanisms is interrogate for differential transcript abundance expression...
Purpose Although a familial distribution has been documented, the genetic aetiology of mitral valve prolapse (MVP) is largely unknown, with only four genes identified so far: FLNA , DCHS1 DZIP1 and PLD1 . The aim this study was to evaluate yield in known causative identify possible novel associated MVP using heart gene panel based on exome sequencing. Methods Patients were referred for counselling when positive family history reported and/or Barlow’s disease diagnosed. In total, 101 probands...
Accurate and consistent interpretation of sequence variants is integral to the delivery safe reliable diagnostic genetic services. To standardize process, in 2015, American College Medical Genetics Genomics (ACMG) Association for Molecular Pathology (AMP) published a joint guideline based on set shared standards classification Mendelian diseases. The generality these their subjective between laboratories has prompted efforts reduce discordance variant classifications, with focus expert...
Abstract Background Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic phenotypic spectrum of KIS yet be the precise mechanism disease fully understood. Methods This study discovers mechanisms underlying (KIS) by describing 15 novel alterations from 47 KIS-affected individuals. We use clinical genetics...
Abstract Genetic missense variants in TNNI3K, encoding troponin‐I interacting kinase, have been associated with dilated cardiomyopathy (DCM) and observed families supraventricular tachycardias (SVT). Previously, a family harboring the TNNI3K ‐c.1615A > G (p.Thr539Ala) variant presented congenital junctional ectopic tachycardia (CJET), an arrhythmia that arises from atrioventricular (AV) node His bundle. However, this was relatively small four‐generational limited genetic testing ( N = 3)....
Hemoglobinopathies, the most common inherited blood disorder, are frequently underdiagnosed. Early identification of carriers is important for genetic counseling couples at risk. The aim this study was to develop and validate a novel machine learning model on multicenter data set, covering wide spectrum hemoglobinopathies based routine complete count (CBC) testing.
The long QT syndrome (LQTS) is an inherited cardiac arrhythmia characterized by a prolonged heart rate–corrected interval (QTc) on the surface electrocardiogram (ECG). It associated with syncope and sudden death from torsades de pointes, estimated to affect 1 per 2000 individuals.1 Fifteen genes have been implicated in familial LQTS, most of which encode ion channels or channel-interacting proteins.2 To date, mutations KCNQ1, KCNH2, SCN5A (causing LQTS 1, 2, 3) found about 70% cases, while...
Unstable hemoglobinopathies (UHs) are rare anemia disorders (RADs) characterized by abnormal hemoglobin (Hb) variants with decreased stability. UHs therefore easily precipitating, causing hemolysis and, in some cases, leading to dominant beta-thalassemia (dBTHAL). The clinical picture of is highly heterogeneous, inheritance pattern dominant, instead recessive as more prevalent major Hb syndromes, and may occur de novo . Most cases not detected conventional testing, diagnosis requires a high...
PurposeBiallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants.MethodsSynthesis of clinical and molecular data concerning 34 five previously reported 12 novel variants, 11 which were functionally characterized.ResultsAmong individuals, only 6 remain...
Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy humans. However, despite knockout mice displaying much more severe with premature death, bi-allelic not yet reported. Here we identify biallelic loss-of-function five unrelated families by next-generation sequencing. In first family, identified compound heterozygous LOF fetus bilateral talipes mild left...
Biallelic loss-of-function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males one female) carrying biallelic variants, including two missense homozygous state LoF were identified by exome sequencing. All had variable degree of developmental delay/intellectual disability microcephaly (ranging from -2.9 SDS to...