L-Type Calcium Channel Mutations in Japanese Patients With Inherited Arrhythmias
L-Type Calcium Channel Mutations in Japanese Patients With Inherited Arrhythmias
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DOI：
10.1253/circj.cj-12-1457
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发表时间：
2013-07-01
影响因子：
3.3
通讯作者：
Horie, Minoru
中科院分区：
文献类型：
--
作者：
Fukuyama, Megumi;Ohno, Seiko;Horie, Minoru
背景资料：编码L型心脏钙通道（LTCC）的基因突变与各种类型的遗传性心律失常有关，包括Brugada综合征（BrS）。然而，亚洲人群中的频率仍然未知。本研究旨在阐明日本患者诊断为BrS或特发性心室颤动（IVF），早期复极综合征，短QT综合征，LTCC相关基因的致病突变，并将其与携带SCN 5A突变的患者进行比较。方法和结果：我们在312名先证者中筛选CACNA 1C和CACNB 2b，并比较先证者与CACNA 1C或SCN 5A基因突变的临床特征。结果，我们在7名无关先证者中发现了6个CACNA 1C突变，在20名先证者中发现了SCN 5A突变。无CACNB 2b突变携带者。在拓扑结构中，一半的突变位于C末端。在7例CACNA 1C突变携带者中，2例为女性，3例有症状; 2例室颤复苏，1例晕厥。与SCN 5A突变携带者相比，其心电图特征无显著性差异。3例有症状的CACNA 1C患者中有2例为女性，但所有女性SCN 5A突变携带者均无症状。结论：我们在BrS和IVF患者中发现了6种CACNA 1C突变，其表型各不相同。虽然突变频率不高，LTCC通道基因的筛选可能是临床上重要的，以防止意外猝死。
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.