L-Type Calcium Channel Mutations in Japanese Patients With Inherited Arrhythmias

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...

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Bibliographic Details
Published in:Circulation Journal 2013, Vol.77(7), pp.1799-1806
Main Authors: Fukuyama, Megumi, Ohno, Seiko, Wang, Qi, Kimura, Hiromi, Makiyama, Takeru, Itoh, Hideki, Ito, Makoto, Horie, Minoru
Format: Article
Language:English
Subjects:
Adult
Arrhythmia
Arrhythmias, Cardiac
Asian Continental Ancestry Group
Brugada syndrome
Calcium channel
Calcium Channels, L-Type - genetics
Female
Genetic Diseases, Inborn - genetics
Genetic Diseases, Inborn - mortality
Genetic Diseases, Inborn - physiopathology
Genetics
Humans
Idiopathic ventricular fibrillation (IVF)
Japan
Male
Middle Aged
Mutation
NAV1.5 Voltage-Gated Sodium Channel - genetics
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Summary: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. Methods and 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.  (Circ J 2013; 77: 1799–1806)
ISSN:1346-9843
1347-4820
DOI:10.1253/circj.CJ-12-1457