title: L-type calcium channel mutations in Japanese patients with inherited arrhythmias.
abstract: BACKGROUND
  Mutations in genes encoding the L-type cardiac calcium channel (LTCC) are associated with various types of inherited arrhythmias, including Brugada syndrome (BrS). However, the frequency in Asian populations remains unknown. This study aimed to elucidate disease-causing mutations in LTCC-related genes in Japanese patients diagnosed as BrS or idiopathic ventricular fibrillation (IVF), early repolarization syndrome, short QT syndrome, and compare them with those carrying SCN5A mutations.
  
  
  RESULTS
  We screened CACNA1C and CACNB2b in 312 probands and compared the clinical characteristics between probands with gene mutations in CACNA1C or SCN5A. In results, we identified 6 CACNA1C mutations in 7 unrelated probands and SCN5A mutations in 20 probands. There were no CACNB2b mutation carriers. In topology, half of the mutations were located in the C-terminus. Among 7 CACNA1C mutation carriers, 2 were female and 3 were symptomatic; 2 patients were resuscitated from ventricular fibrillation, and 1 patient had syncope. Compared with SCN5A mutation carriers, there were no significant differences in the ECG characteristics. 2 of 3 symptomatic CACNA1C patients were female, but all female SCN5A mutation carriers remained asymptomatic.
  
  
  CONCLUSIONS
  We identified 6 CACNA1C mutations in BrS and IVF patients and their phenotypes were varied. Although mutation frequency was not high, screening of LTCC channel genes may be clinically important to prevent unexpected sudden death.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Fukuyama
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kimura
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Itoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac; D044466:Asian People; D020746:Calcium Channels, L-Type / Q000235:genetics*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics
chemical_list: C079146:CACNA1C protein, human; C107597:CACNB2 protein, human; D020746:Calcium Channels, L-Type; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human