A5011541128- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Ion channel regulation and function
- Cardiovascular Effects of Exercise
- Cardiac pacing and defibrillation studies
- Congenital heart defects research
- Receptor Mechanisms and Signaling
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Neuroscience and Neural Engineering
- Viral Infections and Immunology Research
- Cardiac Arrhythmias and Treatments
- ECG Monitoring and Analysis
- Cardiovascular Function and Risk Factors
- Genomics and Rare Diseases
- Signaling Pathways in Disease
- Cardiac Imaging and Diagnostics
- Pulmonary Hypertension Research and Treatments
- Genomic variations and chromosomal abnormalities
- Muscle Physiology and Disorders
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- interferon and immune responses
- Skin and Cellular Biology Research
- Neurogenetic and Muscular Disorders Research
University Hospital Münster
2015-2024
Institut für Forensische Genetik
2015-2022
ERN GUARD-Heart
2020
Heart and Diabetes Center North Rhine-Westphalia
2013
Ruhr University Bochum
2013
University Hospitals of the Ruhr-University of Bochum
2010
Long QT syndromes (LQTS) are heritable diseases characterized by prolongation of the interval on an electrocardiogram, which often leads to syncope and sudden cardiac death. Here we report generation induced pluripotent stems (iPS) cells from two patients with LQTS type 3 carrying a different point mutation in sodium channel Nav1.5 (p.V240M p.R535Q) functional characterization cardiomyocytes (CM) derived them. The iPS exhibited all characteristic properties stem cells, maintained...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate features of ion channel mutations causing inherited rhythm disease. However, the lack maturity these cells is considered a significant limitation model. Prolonged culture hiPSC-CMs promotes maturation cells. We studied electrophysiological effects I230T mutation in sodium gene SCN5A generated from homozygous (I230Thomo) and heterozygous (I230Thet) individual family with recessive cardiac conduction Since...
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...
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...
Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration.Patients either presumed autosomal dominant (N = 229) or recessive Type 2 Jervell Lange-Nielsen 19) were enrolled from 22 arrhythmia clinics 4 registries 9 countries. evaluated for ECG penetrance (defined as QTc...
Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 ECG often transient, genetic cause only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present BrS, we evaluated whether autoantibodies can detected these
A variant in the SLC4A3 anion exchanger has been identified as a novel cause of short QT syndrome (SQTS), but clinical importance SQTS or sudden cardiac death remains unknown.
Background: Familial atrial septal defect (ASD) has previously been attributed primarily to mutations in cardiac transcription factors. Here, we report a large, multi-generational family (78 members) with ASD combined late-onset dilated cardiomyopathy and further characterize the consequences of mutant α-actin. Methods: We genome-wide linkage analysis cell biology, microscopy, molecular biology tools novel ACTC1 (cardiac α-actin) mutation identified association family. Results: Using...
The long-QT syndrome (LQTS) is the most common ion channelopathy, typically presenting with a prolonged QT interval and clinical symptoms such as syncope or sudden cardiac death. Patients may present concealed phenotype making diagnosis challenging. Correctly diagnosing at-risk patients pivotal to starting early preventive treatment.Identification of congenital often LQTS by utilizing novel deep learning network architectures, which are specifically designed for multichannel time series...
Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but also expressed postsynaptically neurons. So far, homozygous loss of function mutations CACNA1D encoding the α1-subunit described congenital sinus node dysfunction deafness. In addition, germline have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability primary hyperaldosteronism. Here, a three-generation family with...
Risk assessment for life-threatening arrhythmias in congenital Long QT Syndrome (LQTS) is still imprecise. The repolarizing current Iks encoded by KCNQ1 (LQT1) increases during exercise, and thus plays an important role shortening the interval increased heart rate. Accordingly, LQTS patients, particularly those with LQT1, are at high arrhythmic risk exercise.
The heterozygous mutation c.155G > T in GNB2 clinically leads to sinus bradycardia and node dysfunction. Here, patient-specific skin fibroblasts of the carrier were used for Sendai virus reprogramming into human induced-pluripotent stem cells (hiPSC). For generating isogenic control cell line, a CRISPR/Cas9-mediated HDR-repair hiPSCs was carried out. Both generated lines (GNB2 SV5528, K26) maintained normal karyotype, morphology pluripotency immunofluoresence RT-qPCR analysis. hiPSC-lines...
A published heterozygous gain-of-function variant in the KCNJ5 gene (p.Trp101Cys) encoding G-protein-activated inward-rectifier potassium channel 4 subunit of IK,ACh is associated with human sinus node dysfunction (SND). Differentiated hiPSC-cardiomyocytes may serve as an in-vitro model to study SND and develop pharmacological rescue strategies. Therefore, a mutant hiPSCs line from patient-derived peripheral blood mononuclear cells (PBMCs) were reprogrammed CytoTune-iPS 2.0 Sendai...
Mutations in the KCNJ5 gene, encoding one of major subunits cardiac G-protein-gated inwardly rectifying K+ (GIRK) channels, have been recently linked to inherited forms sinus node dysfunction. Here, pathogenic mechanism W101C mutation underlying bradycardia a patient-derived cellular disease model dysfunction (SND) was investigated. A human-induced pluripotent stem cell (hiPSCs) line carrier generated, and CRISPR/Cas9-based gene targeting used correct familial as control line. Both lines...
We recently reported a novel, heterozygous, and non-synonymous ACTC1 mutation (p.Gly247Asp or G247D) in large, multi-generational family, causing atrial-septal defect followed by late-onset dilated cardiomyopathy (DCM). also found that the G247D negatively regulated serum response (SRF)-signaling thereby contributing to DCM observed human patients carrying this ("A cardiac α-actin (ACTC1) p. Gly247Asp inhibits SRF-signaling vitro neonatal rat cardiomyocytes" [1]). There are some mutations...