Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.
Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.
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DOI：
10.1016/j.hrthm.2010.08.026
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发表时间：
2010-12
期刊：
影响因子：
5.5
通讯作者：
Antzelevitch, Charles
中科院分区：
文献类型：
--
作者：
Burashnikov, Elena;Pfeiffer, Ryan;Barajas-Martinez, Hector;Delpon, Eva;Hu, Dan;Desai, Mayurika;Borggrefe, Martin;Haeissaguerre, Michel;Kanter, Ronald;Pollevick, Guido D.;Guerchicoff, Alejandra;Laino, Ruben;Marieb, Mark;Nademanee, Koonlawee;Nam, Gi-Byoung;Robles, Roberto;Schimpf, Rainer;Stapleton, Dwight D.;Viskin, Sami;Winters, Stephen;Wolpert, Christian;Zimmern, Samuel;Veltmann, Christian;Antzelevitch, Charles
l型钙通道（LTCC）突变与Brugada综合征（BrS）、短QT间期综合征（SQT）和Timothy综合征（LQT8）有关。LTCC突变在多大程度上导致与心源性猝死相关的j波综合征，目前所知甚少。本研究的目的是在205例被诊断为BrS、特发性心室颤动（IVF）和早期复极综合征（ERS）的先证者中鉴定LTCC (Cav1.2) α1、β2和α2δ亚基突变。对162例BrS和BrS+SQT先证者，19例IVF先证者，24例ERS先证者的CACNA1C、CACNB2b和CACNA2D1基因进行直接测序筛选。总共鉴定出23个不同的突变。分别有12.3%、5.2%和16%的BrS/BrS+SQT、IVF和ERS先证显示LTCC α1、β2和α2δ亚基突变。当纳入罕见多态性时，BrS/BrS+SQT、IVF和ERS先证的产量分别提高到17.9%、21%和29.1%。与BrS和BrS+SQT相关的两种CACNA1C突变的功能性表达导致钙通道电流功能丧失。显示正常QTc的BrS先证者有已知延长QT间期的额外变异。研究结果表明，在与遗传性心律失常相关的j波综合征的先证者中检测到ltcc突变的比例很高，这表明Cav基因的遗传筛查可能是识别高危个体的有价值的诊断工具。这些结果首次确定了CACNA2D1是一种新的BrS易感基因，CACNA1C、CACNB2和CACNA2D1可能是新的ERS易感基因。
L-type calcium channel (LTCC) mutations have been associated with Brugada syndrome (BrS), short QT (SQT) syndrome, and Timothy syndrome (LQT8). Little is known about the extent to which LTCC mutations contribute to the J-wave syndromes associated with sudden cardiac death. The purpose of this study was to identify mutations in the α1, β2, and α2δ subunits of LTCC (Cav1.2) among 205 probands diagnosed with BrS, idiopathic ventricular fibrillation (IVF), and early repolarization syndrome (ERS). CACNA1C, CACNB2b, and CACNA2D1 genes of 162 probands with BrS and BrS+SQT, 19 with IVF, and 24 with ERS were screened by direct sequencing. Overall, 23 distinct mutations were identified. A total of 12.3%, 5.2%, and 16% of BrS/BrS+SQT, IVF, and ERS probands displayed mutations in α1, β2, and α2δ subunits of LTCC, respectively. When rare polymorphisms were included, the yield increased to 17.9%, 21%, and 29.1% for BrS/BrS+SQT, IVF, and ERS probands, respectively. Functional expression of two CACNA1C mutations associated with BrS and BrS+SQT led to loss of function in calcium channel current. BrS probands displaying a normal QTc had additional variations known to prolong the QT interval. The study results indicate that mutations in the LTCCs are detected in a high percentage of probands with J-wave syndromes associated with inherited cardiac arrhythmias, suggesting that genetic screening of Cav genes may be a valuable diagnostic tool in identifying individuals at risk. These results are the first to identify CACNA2D1 as a novel BrS susceptibility gene and CACNA1C, CACNB2, and CACNA2D1 as possible novel ERS susceptibility genes.
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影响因子：
5.5
作者：
Kapplinger, Jamie D.;Tester, David J.;Salisbury, Benjamin A.;Carr, Janet L.;Harris-Kerr, Carole;Pollevick, Guido D.;Wilde, Arthur A. M.;Ackerman, Michael J.
通讯作者：
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影响因子：
37.8
作者：
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通讯作者：
Ackerman MJ
影响因子：
5.5
作者：
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通讯作者：
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DOI：
10.1046/j.1540-8167.2001.01223.x
发表时间：
2001-11-01
影响因子：
2.7
作者：
Kubota, T;Horie, M;Sasayama, S
通讯作者：
Sasayama, S
影响因子：
37.8
作者：
Antzelevitch, Charles;Pollevick, Guido D.;Wolpert, Christian
通讯作者：
Wolpert, Christian