Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease.
Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease.
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DOI：
10.1002/humu.9144
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发表时间：
2003-06-01
期刊：
影响因子：
3.9
通讯作者：
Haverkamp, Wilhelm
中科院分区：
文献类型：
--
作者：
Schulze-Bahr, Eric;Eckardt, Lars;Haverkamp, Wilhelm
Brugada综合征（BS）是特发性心室颤动的一种特殊形式，可导致健康年轻人的心源性猝死。在体表心电图上，非典型右束分支阻滞和右心前导联st段抬高可识别BS。目前只知道心脏钠通道基因SCN5A的突变会导致BS。在多中心的努力下，我们收集了44名不相关指数患者及其家庭成员的临床数据，并对SCN5A进行了完整的遗传分析。37%的患者为家族性，而大多数患者为散发性（63%）。发现了5个新的SCN5A突变（2602delC，导致：E867X； 2581_2582del TT: F861fs951X; 2673G>A: E1225K; 4435_4437delAAG: K1479del; 5425C>A: S1812X），随机分布在SCN5A中。突变频率（SCN5A+）在家族性疾病（38%）和散发疾病（0%）之间存在显著差异（p=0.001）。SCN5A+成人患者的疾病外显率是完全的，而SCN5A+儿童患者的疾病外显率是不完全的（17%）。SCN5A基因检测在家族性疾病中特别有用，可以识别有心脏风险的个体。然而，在散发病例中，基因基础和突变筛查的价值必须进一步确定。这些结果可能与BS的遗传和临床异质性一致。
The Brugada syndrome (BS) is a distinct form of idiopathic ventricular fibrillation and may cause sudden cardiac death in healthy young individuals. In the surface ECG, BS can be recognized by an atypical right bundle branch block and ST-segment elevation in the right precordial leads. Mutations in the cardiac sodium channel gene SCN5A are only known to cause BS. In a multi-center effort, we have collected clinical data on 44 unrelated index patients and family members and performed a complete genetic analysis of SCN5A. In 37% the disease was familial, whereas in the majority it was sporadic (63%). Five novel SCN5A mutations (2602delC, resulting in: E867X; 2581_2582del TT: F861fs951X; 2673G>A: E1225K; 4435_4437delAAG: K1479del; and 5425C>A: S1812X) were found and were randomly located in SCN5A. Mutation frequencies (SCN5A+) differed significantly between familial (38%) and sporadic disease (0%) (p=0.001). Disease penetrance was complete in the SCN5A+ adult patients, but incomplete in SCN5A+ children (17%). Genetic testing of SCN5A is especially useful in familial disease to identify individuals at cardiac risk. In sporadic cases, however, a genetic basis and the value of mutation screening has to be further determined. These results are in line with a possibly genetic and clinical heterogeneity of BS.