title: Novel SCN10A variants associated with Brugada syndrome.
abstract: OBJECTIVE
  The expression of sodium channel Nav1.8 in cardiac nervous systems has been identified, and variants of SCN10A that encodes Nav1.8 contribute to the development of Brugada syndrome (BrS) by modifying the function of Nav1.5 or directly reducing the sodium current. The aim of this study was to identify the frequency of SCN10A mutations in Japanese patients with BrS and to compare the phenotypical differences between patients with BrS and those who have other BrS-causative genes.
  
  
  RESULTS
  This study involved 240 Japanese probands who were clinically suspected with BrS and were negative for mutations in major BrS-related genes. We screened for the SCN10A gene using a high-resolution melting method and direct sequencing. In addition, we compared the clinical characteristics among the probands with gene mutations in SCN10A, 6 probands with CACNA1C and 17 probands with SCN5A. We identified six SCN10A variant carriers (2.5%): W189R, R844H (in two unrelated probands), N1328K, R1380Q, and R1863Q. Five were male. Four were symptomatic: one died following sudden cardiopulmonary arrest at age 35, one suffered ventricular fibrillation, and two had recurrent syncope. Compared with BrS patients carrying SCN5A or CACNA1C mutations, although there were no significant differences among them, symptomatic patients in the SCN10A group tended to be older than those in the other gene groups.
  
  
  CONCLUSIONS
  In six BrS probands who carried SCN10A variants, most experienced severe arrhythmic attacks. It is of clinical importance to screen SCN10A mutations in BrS, although the functional significance of these variants remains unclear.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Fukuyama
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Shiga, Japan Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan horie@belle.shiga-med.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000328:Adult; D000368:Aged; D053840:Brugada Syndrome / Q000150:complications* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D013575:Syncope / Q000453:epidemiology*; D014693:Ventricular Fibrillation / Q000453:epidemiology*
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human
keywords: Brugada syndrome; Genetics; Nav1.8; SCN10A; Ventricular arrhythmia