Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing.
Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing.
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DOI：
10.1016/j.jacc.2012.04.037
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发表时间：
2012-10-09
影响因子：
24
通讯作者：
Ackerman, Michael J.
中科院分区：
文献类型：
--
作者：
Crotti, Lia;Marcou, Cherisse A.;Tester, David J.;Castelletti, Silvia;Giudicessi, John R.;Torchio, Margherita;Medeiros-Domingo, Argelia;Simone, Savastano;Will, Melissa L.;Dagradi, Federica;Schwartz, Peter J.;Ackerman, Michael J.
提供迄今为止在一个大型BrS队列中发现的12个Brugada综合征（BrS）易感基因的突变谱和患病率。BrS是一种潜在致命的遗传性心律失常综合征，通过心电图诊断为右胸导联（V1-V3; 1型Brugada ECG模式）的覆盖型ST段抬高和存在心脏事件的个人/家族史。使用PCR、DHPLC和DNA测序，对129例可能/很可能BrS的无关患者[46例临床诊断为BrS（ECG模式加上个人/家族心脏事件史）和83例仅1型ECG模式]进行了BrS 1 -12易感基因的综合突变分析。总体而言，27例（21%）患者存在推定的致病性突变，在1400个高加索人参考等位基因中不存在，包括21例SCN 5A突变、2例CACNB 2B、1例KCNJ 8、1例KCND 3、1例SCN 1Bb和1例HCN 4。在仅有1型心电图的患者中，总体突变率为23%，而在临床诊断的BrS患者中为17%，在临床诊断的BrS患者中，年龄< 20岁的年轻男性和PQ间期延长的患者中显著更高。我们在约20%的BrS队列中确定了推定的致病突变，其中BrS 2 -12占<5%。重要的是，仅具有1型BrS心电图模式的患者与临床确诊BrS的患者之间的产率相似。当PQ间隔超过200 ms时，SCN 5A介导的BrS（BrS 1）的产率接近40%。在没有短QT间期的情况下，钙通道介导的BrS极不可能发生。
To provide the spectrum and prevalence of mutations in the 12 Brugada Syndrome (BrS)-susceptibility genes discovered to date, in a single large BrS cohort. BrS is a potentially lethal heritable arrhythmia syndrome diagnosed electrocardiographically by coved-type ST segment elevation in the right precordial leads (V1-V3; type-1 Brugada ECG pattern) and the presence of a personal/family history of cardiac events. Using PCR, DHPLC, and DNA sequencing, comprehensive mutational analysis of BrS1-12-susceptibility genes was performed in 129 unrelated patients with possible/probable BrS [46 with clinically diagnosed BrS (ECG pattern plus personal/family history of a cardiac event) and 83 with type 1 ECG pattern only]. Overall, 27 (21%) patients had a putative pathogenic mutation, absent in 1400 Caucasian reference alleles, including 21 patients with an SCN5A mutation, 2 CACNB2B, 1 KCNJ8, 1 KCND3, 1 SCN1Bb, and 1 HCN4. The overall mutation yield was 23% in type 1 ECG pattern only patients versus 17% in clinically diagnosed BrS patients, was significantly greater among young men < 20 years of age with clinically diagnosed BrS, and among patients who had a prolonged PQ interval. We identified putative pathogenic mutations in ~20% of our BrS cohort, with BrS2-12 accounting for < 5%. Importantly, the yield was similar between patients with only a type 1 BrS ECG pattern and those with clinically established BrS. The yield approaches 40% for SCN5A-mediated BrS (BrS1) when the PQ interval exceeds 200ms. Calcium channel-mediated BrS is extremely unlikely in the absence of a short QT interval.
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影响因子：
5.5
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
通讯作者：
Antzelevitch, Charles
影响因子：
8.4
作者：
Delpon, Eva;Cordeiro, Jonathan M.;Antzelevitch, Charles
通讯作者：
Antzelevitch, Charles
影响因子：
6.2
作者：
Gollob, Michael H.;Blier, Louis;Woo, Anna
通讯作者：
Woo, Anna
影响因子：
5.5
作者：
Giudicessi, John R.;Ye, Dan;Tester, David J.;Crotti, Lia;Mugione, Alessandra;Nesterenko, Vladislav V.;Albertson, Richard M.;Antzelevitch, Charles;Schwartz, Peter J.;Ackerman, Michael J.
通讯作者：
Ackerman, Michael J.
影响因子：
37.8
作者：
Kapa S;Tester DJ;Salisbury BA;Harris-Kerr C;Pungliya MS;Alders M;Wilde AA;Ackerman MJ
通讯作者：
Ackerman MJ