title: Phenotypical manifestations of mutations in the genes encoding subunits of the cardiac sodium channel.
abstract: Variations in the gene encoding for the major sodium channel (Na(v)1.5) in the heart, SCN5A, has been shown to cause a number of arrhythmia syndromes (with or without structural changes in the myocardium), including the long-QT syndrome (type 3), Brugada syndrome, (progressive) cardiac conduction disease, sinus node dysfunction, atrial fibrillation, atrial standstill, and dilated cardiomyopathy. Of equal importance are variations in genes encoding for various subunits and regulatory proteins interacting with the α-subunit Na(v)1.5 and modifying its function. Based on detailed studies of genotype-phenotype relationships in these disease entities, on detailed studies of the basic electrophysiological phenotypes (heterologous expressed wild-type and mutant sodium channels and their interacting proteins), and on attempts to integrate the obtained knowledge, the past 15 years has witnessed an explosion of knowledge about these disease entities.
authors: Department of Clinical and Experimental Cardiology, Academic Medical Center, University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.a.wilde@amc.uva.nl
authors: Arthur A M
authors: AA
authors: Wilde
authors: Ramon
authors: R
authors: Brugada
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000502:physiology; D051244:Caveolin 3 / Q000502:physiology; D005993:Glycerolphosphate Dehydrogenase / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics* / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D051244:Caveolin 3; D008565:Membrane Proteins; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; C091825:syntrophin alpha1; D005993:Glycerolphosphate Dehydrogenase