Articles: nav1-5-voltage-gated-sodium-channel.
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Case Reports
SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the activation gating of NaV1.5 channel.
Brugada syndrome (BrS) is an inherited lethal arrhythmic disorder characterized by syncope and sudden cardiac death from ventricular tachyarrhythmias. Here we identified a novel K817E mutation of SCN5A gene in a man with type 1 BrS electrocardiogram pattern using next-generation sequencing targeted for 73 cardiac disorder-related genes. SCN5A encodes the α-subunit of NaV1.5 voltage-gated Na(+) channel, and some of its mutations are linked to BrS. The proband had no mutation in any of the other arrhythmia-related genes sequenced. ⋯ The K817E mutation of SCN5A gene leads to loss of function of NaV1.5 channel and may underlie the BrS phenotype of the proband.
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A major goal of precision medicine is to improve disease prevention and therapy by using big data provided by genomic technology and electronic health records. In a new study, assessment of a patient population without a history of cardiac disease revealed that genetic variants putatively associated with a risk of sudden death were not linked with arrhythmia phenotypes.
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Naunyn Schmiedebergs Arch. Pharmacol. · Mar 2016
Inhibition of the cardiac Na(+) channel α-subunit Nav1.5 by propofol and dexmedetomidine.
Propofol and dexmedetomidine are very commonly used sedative agents. However, several case reports demonstrated cardiovascular adverse effects of these two sedatives. Both substances were previously demonstrated to quite potently inhibit neuronal voltage-gated Na(+) channels. ⋯ Dexmedetomidine was generally more potent as compared to propofol. Propofol and dexmedetomidine seem to interact with the LA-binding site to inhibit the cardiac Na(+) channel Nav1.5 in a state-dependent manner. These data suggest that Nav1.5 is a hitherto unrecognized molecular component of some cardiovascular side effects of these sedative agents.
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Multicenter Study
Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.
Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. ⋯ Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings.