title: The role of mutations in the SCN5A gene in cardiomyopathies.
abstract: The SCN5A gene encodes the alpha-subunit of the Nav1.5 ion channel protein, which is responsible for the sodium inward current (INa). Since 1995 several hundred mutations in this gene have been found to be causative for inherited arrhythmias including Long QT syndrome, Brugada syndrome, cardiac conduction disease, sudden infant death syndrome, etc. As expected these syndromes are primarily electrical heart diseases leading to life-threatening arrhythmias with an "apparently normal heart". In 2003 a new form of dilated cardiomyopathy was identified associated with mutations in the SCN5A gene. Recently mutations have been also found in patients with arrhythmogenic right ventricular cardiomyopathy and atrial standstill. The purpose of this review is to outline and analyze the following four topics: 1) SCN5A genetic variants linked to different cardiomyopathies; 2) clinical manifestations of the known mutations; 3) possible molecular mechanisms of myocardial remodeling; and 4) the potential implications of gene-specific treatment for those disorders. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
authors.affiliation: Petrovsky Russian Research Centre of Surgery, Abricosovsky pereulok, 119991 Moscow, Russia; Department of Molecular and Cellular Genetics, Pirogov Russian National Research Medical University, Ostrovityanova str. 1, Moscow 117997, Russia. Electronic address: zhelene@mail.ru.
authors.forename: Elena
authors.initials: E
authors.lastname: Zaklyazminskaya
authors.affiliation: Petrovsky Russian Research Centre of Surgery, Abricosovsky pereulok, 119991 Moscow, Russia. Electronic address: sdzemeshkevich@gmail.com.
authors.forename: Sergei
authors.initials: S
authors.lastname: Dzemeshkevich
mesh_terms: D000200:Action Potentials; D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012307:Risk Factors; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D005819:Genetic Markers; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: Arrhythmogenic right ventricular cardiomyopathy; Cardiac remodeling; Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Na(v)1.5; SCN5A