A5072697496- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Sports injuries and prevention
- Congenital heart defects research
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Viral Infections and Immunology Research
- Cardiovascular Syncope and Autonomic Disorders
- Cardiac Arrest and Resuscitation
- RNA Research and Splicing
- Cardiac pacing and defibrillation studies
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Congenital Heart Disease Studies
- Genomics and Rare Diseases
- Skin and Cellular Biology Research
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Cardiac Imaging and Diagnostics
- Cardiac Structural Anomalies and Repair
- Neurology and Historical Studies
Universitätsklinikum Würzburg
2016-2025
Comprehensive Cancer Center Mainfranken
2017-2025
University of Calgary
2012-2023
University of Würzburg
2019-2023
Libin Cardiovascular Institute of Alberta
2012-2023
Institute of Solution Chemistry
2019
Washington University in St. Louis
2017
Leiden University
2017
Johns Hopkins Hospital
2017
Hospital General Universitario Gregorio Marañón
2017
Left ventricular noncompaction constitutes a primary cardiomyopathy characterized by severely thickened, 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. The genetic basis of this is still largely unresolved. We speculated that mutations in sarcomere protein genes known to cause hypertrophic dilated may be associated with left noncompaction.Mutational analysis cohort 63 unrelated adult probands no other congenital heart anomalies was performed...
Individuals affected by restrictive cardiomyopathy (RCM) often develop heart failure at young ages resulting in early transplantation. Familial forms are mainly caused mutations sarcomere proteins and demonstrate a common genetic etiology with other inherited cardiomyopathies. Using next-generation sequencing, we identified two novel missense variants (p.S1624L; p.I2160F) filamin-C (FLNC), an actin-cross-linking protein expressed skeletal muscle, segregating families autosomal-dominant RCM....
Abstract Frameshift mutations in the TTN gene encoding titin are a major cause for inherited forms of dilated cardiomyopathy ( DCM ), heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive failure. To date, there no specific treatment options patients but transplantation. Here, we show beneficial potential reframing transcripts antisense oligonucleotide AON )‐mediated exon skipping human murine models carrying previously identified autosomal‐dominant...
Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role genetic testing in survivors without a definite clinical phenotype is unclear.The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) large registry where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 from 2006 to 2015, 174 underwent testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative...
Isolated noncompaction of the ventricular myocardium (INVM, MIM 300183 and 604169) is a congenital unclassified cardiomyopathy with numerous prominent trabeculations deep intertrabecular recesses in hypertrophied hypokinetic myocardium. Mutations G4.5 gene result wide spectrum severe infantile X-linked cardiomyopathic phenotypes including Barth syndrome dilated INVM. Molecular genetic analysis INVM has only been performed pediatric patients. Although adult patients show similar cardiac...
Left ventricular noncompaction (LVNC) is a congenital unclassified cardiomyopathy with numerous prominent trabeculations and deep intertrabecular recesses in hypertrophied hypokinetic myocardium. It has been reported to occur isolation or association heart disease. Mutations the X-linked G4.5 gene are responsible for cases of isolated LVNC male infants, but mutations were not found patients clinical onset disease adulthood. In addition, several families an autosomal dominant pattern...
The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients apparently unexplained cardiac arrest and no evident disease to identify the pathogenesis of through systematic clinical testing. Exercise testing, drug provocation, advanced imaging, genetic testing may be useful when a cause is not apparent.The first 200 survivors from 14 centers across Canada were evaluated determine results investigation follow-up (age, 48.6±14.7 years, 41% female). Patients...
Here, we present a small Iranian family, where the index patient received diagnosis of restrictive cardiomyopathy (RCM) in combination with atrioventricular (AV) block. Genetic analysis revealed novel homozygous missense mutation DES gene (c.364T > C; p.Y122H), which is absent human population databases. The localized highly conserved coil-1 desmin subdomain. In silico, prediction tools indicate deleterious effect (DES) p.Y122H. Consequently, generated an expression plasmid encoding mutant...
Background Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion cardiomyocytes; however, the molecular cellular mechanisms underlying disease remain widely unknown. Desmocollin-2 cadherin serving anchor molecule required reconstitute homeostatic intercellular with desmoglein-2. Cardiac specific lack desmoglein-2...
Background— Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for abnormalities. Methods and Results— Around 398 family members (186 UCA, 212 victims’ relatives; mean age, 44±17 years) underwent extensive workup, including ECG, signal averaged exercise testing, imaging, Holter-monitoring,...
Desmosome diseases are caused by dysfunction of desmosomes, which anchor intermediate filaments (IFs) at sites cell-cell adhesion. For many decades, the focus attention has been on role actin filament-associated adherens junctions in development and disease, especially cancer. However, interference with function their molecular constituents or attachments to IFs now emerged as a major contributor variety affecting different tissues organs including skin, heart digestive tract. The first...
Nuclear envelope proteins play an important role in the pathogenesis of hereditary cardiomyopathies. Recently, a new form arrhythmic cardiomyopathy caused by homozygous mutation (p.L13R) inner nuclear membrane protein LEMD2 was discovered. The aim to unravel molecular mechanisms mutant cardiomyopathy.We generated Lemd2 p.L13R knock-in mouse model and corresponding cell via CRISPR/Cas9 technology investigated cardiac phenotype as well cellular subcellular rupture repair.Knock-in mice...
Dominant mutations in cellular junction proteins are the major cause of arrhythmogenic cardiomyopathy, whereas recessive those cardiocutaneous syndromes such as Naxos and Carvajal syndrome. The Hutterites distinct genetic isolates who settled North America 1874. Descended from <100 founders, they trace their origins to 16th-century Europe.We clinically genetically evaluated 2 large families Alberta Hutterite population with a history sudden death found several individuals severe forms...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder mainly caused by dominant mutations in several components of the desmosome including plakophilin-2 (PKP2), most prevalent disease gene. Little known about underlying genetic and molecular mechanisms missense located armadillo (ARM) domains PKP2, as well their consequences on human pathology.We focused vivo vitro studies PKP2 founder mutation c.2386T>C (p.C796R), demonstrated tissue from 2 related carriers...