摘要
自从心脏钠离子通道 基因 (SC N 5A )突变 被首次鉴定 以来,人们对 SC N 5A 突变进行 了一系列研 究.SC N 5A突 变是在 两种明 显不同但 都与突 发性死 亡相关 联的疾病 ———长 Q T 波综合 症 (LQ T3)的 一种形 式和 B rugada 综合症 中被 鉴定的.后来 ,Lev-Lenegre 综 合症 进行 性的 心脏传 导缺 陷)也增 加到 LQ T3中.基因型 和表 型相 互关 系的 (研 究以及体外 表达研究提 供证据认为 SC N 5A 蛋白的结构 和功能相互 关系远比最 初预期的复 杂.心脏钠通 道的生物 物理特征与不同 的表型相关, 基因型和表型 相互关系的研究 使我们注意到 即使是单个 氨基酸的置换 都可能显而 易见的影响心脏 的兴奋性 .由 隐藏有 SC N 5A 突变的病 人提供的证 据以及临床呈 现 “重叠”现象的证 据显示已经 需要对上述提及 的疾病的传统 分类进行修改 .现在认为 钠通道综合症”作 为唯一的临 床称谓表示这 类疾病可 “能 的表型范围更合 适 .
A very active line of research took place after the first identification of SCN5A mutations.Mutations in SCN5A have been identified in 2 distinct diseases associated with sudden death: one form of the long QT syndrome (LQT3) and the Brugada syndrome. Subsequently, the Lev Lenegre syndrome (progressive cardiac conduction defect)was additional to LQT3 . Genotype phenotype correlation and in vitro expression studies provide evidence that structure function relationships of the SCN5A protein are much more complex than initially anticipated. The biophysical characterization of the sodium channel defects associated with different phenotypes and the genotype phenotype correlation studies brought to the attention of the scientific community a plethora of mechanisms by which even a single amino acid substitution may remarkably affect cardiac excitability. The evidence of patients harboring an SCN5A mutation and overlapping clinical presentations creates a need for a revision of the traditional classification of the above mentioned diseases. It is now appropriate to consider the 'sodium channel syndrome' as a unique clinical entity that may manifest itself with a spectrum of possible phenotypes.
出处
《生命科学研究》
CAS
CSCD
2004年第S1期18-23,共6页
Life Science Research
基金
国家自然科学基金资助项目(3017049
30370644
30213904)
教育部重点课题项目(02A 028)
湖南省教育厅项目(02B017)
