Novel SCN10A variants associated with Brugada syndrome
Novel SCN10A variants associated with Brugada syndrome
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DOI：
10.1093/europace/euv078
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发表时间：
2016-06-01
期刊：
影响因子：
6.1
通讯作者：
Horie, Minoru
中科院分区：
文献类型：
--
作者：
Fukuyama, Megumi;Ohno, Seiko;Horie, Minoru
钠通道Na（v）1.8在心脏神经系统中的表达已经被鉴定，并且编码Na（v）1.8的SCN 10A的变体通过改变Na（v）1.5的功能或直接降低钠电流而促成Brugada综合征（BrS）的发展。本研究的目的是确定的频率SCN 10A突变的日本患者与BrS和那些谁有其他BrS-causative gene.This study involved 240日本先证者临床怀疑与BrS和主要BrS相关基因突变阴性的BrS患者之间的表型差异进行比较。我们使用高分辨率熔解方法和直接测序筛选SCN 10A基因。此外，我们还比较了SCN 10A基因突变先证者、6例CACNA 1C先证者和17例SCN 5A先证者的临床特征。我们确定了六个SCN 10A变异携带者（2.5%）：W189 R，R844 H（在两个不相关的先证者中），N1328 K，R1380 Q和R1863 Q。5人为男性。四个有症状：一人在35岁时死于心肺骤停，一人患有心室纤维性颤动，两人反复晕厥。与携带SCN 5A或CACNA 1C突变的BrS患者相比，虽然他们之间没有显著差异，但SCN 10A组的症状患者往往比其他基因组的患者年龄大。在BrS中筛选SCN 10A突变具有临床重要性，尽管这些变体的功能意义尚不清楚。
The expression of sodium channel Na(v)1.8 in cardiac nervous systems has been identified, and variants of SCN10A that encodes Na(v)1.8 contribute to the development of Brugada syndrome (BrS) by modifying the function of Na(v)1.5 or directly reducing the sodium current. The aim of this study was to identify the frequency of SCN10A mutations in Japanese patients with BrS and to compare the phenotypical differences between patients with BrS and those who have other BrS-causative genes.This study involved 240 Japanese probands who were clinically suspected with BrS and were negative for mutations in major BrS-related genes. We screened for the SCN10A gene using a high-resolution melting method and direct sequencing. In addition, we compared the clinical characteristics among the probands with gene mutations in SCN10A, 6 probands with CACNA1C and 17 probands with SCN5A. We identified six SCN10A variant carriers (2.5%): W189R, R844H (in two unrelated probands), N1328K, R1380Q, and R1863Q. Five were male. Four were symptomatic: one died following sudden cardiopulmonary arrest at age 35, one suffered ventricular fibrillation, and two had recurrent syncope. Compared with BrS patients carrying SCN5A or CACNA1C mutations, although there were no significant differences among them, symptomatic patients in the SCN10A group tended to be older than those in the other gene groups.In six BrS probands who carried SCN10A variants, most experienced severe arrhythmic attacks. It is of clinical importance to screen SCN10A mutations in BrS, although the functional significance of these variants remains unclear.