Dagmar I. Keller

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Laminopathies are a group of disorders caused by mutations in the LMNA gene encoding A-type lamins, components of the nuclear lamina. Three of these disorders affect specifically the skeletal and/or cardiac muscles, and their pathogenic mechanisms are still unknown. We chose the LMNA H222P missense mutation identified in a family with autosomal dominant(More)
More than 70 drugs present on the Swiss market can cause drug-induced long QT syndrome (LQTS), which is associated with torsades de pointes (TdP) arrhythmias, potentially leading to sudden cardiac death. Basic and clinical investigations performed during the last decade have helped a better understanding of the mechanisms and risk factors of this serious(More)
OBJECTIVE Cardiac myosin-binding protein C (cMyBP-C) gene mutations are involved in familial hypertrophic cardiomyopathy (FHC). Many of these mutations produce truncated proteins, which are unstable in the cardiac tissue of patients, suggesting that haploinsufficiency could account for the development of the phenotype. However, existing mouse models of(More)
OBJECTIVE Brugada syndrome (BrS) is characterized by ventricular tachyarrhythmias leading to sudden cardiac death and is caused, in part, by mutations in the SCN5A gene encoding the sodium channel Na(v)1.5. Fever can trigger or exacerbate the clinical manifestations of BrS. The aim of this work was to characterize the genetic and molecular determinants of(More)
AIMS Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135(More)
Inherited long QT syndrome (LQTS) is caused by mutations in six genes including SCN5A, encoding the alpha-subunit of the human cardiac voltage-dependent sodium channel hNa(v)1.5. In LQT3, various mutations in SCN5A were identified, which produce a gain of channel function. The aim of this study was to screen SCN5A for mutations in a family with the LQT3(More)
Familial hypertrophic cardiomyopathy (FHC) is associated with mutations in 11 genes encoding sarcomeric proteins. Most families present mutations in MYBPC3 and MYH7 encoding cardiac myosin-binding protein C and beta-myosin heavy chain. The consequences of MYH7 mutations have been extensively studied at the molecular level, but controversial results have(More)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially fatal disease, which is often difficult to diagnose. As a non-invasive test cardiac magnetic resonance imaging (CMR) has become an important tool in establishing the diagnosis. The aim of this study was to evaluate the diagnostic and prognostic value of CMR in patients with suspected(More)
The human cardiac sodium channel Na(v)1.5 encoded by the SCN5A gene plays a critical role in cardiac excitability and the propagation of action potentials. Na(v)1.5 dysfunctions due to mutations cause cardiac diseases such as the LQT3 form of long QT syndrome, conduction disorders, and Brugada syndrome (BrS). They have also recently been associated with(More)
BACKGROUND Brugada syndrome (BS) is an electrical cardiac disorder with a right bundle branch block and ST segment elevation in leads V1 to V3 on surface electrocardiograms (ECGs), and is a syndrome that may lead to sudden cardiac death. PURPOSE The aim of the present study was to screen for mutations in the SCN5A gene in a family with BS, and to(More)