The Molecular Biology of Genetic-Based Epilepsies
The Molecular Biology of Genetic-Based Epilepsies
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遗传性癫痫的分子生物学
DOI：
10.1007/s12035-013-8523-6
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发表时间：
2014-02-01
影响因子：
5.1
通讯作者：
Song, Zhi
中科院分区：
文献类型：
--
作者：
Deng, Hao;Xiu, Xiaofei;Song, Zhi
癫痫是一种以中枢神经系统异常电活动为特征的最常见的神经系统疾病。这种疾病的临床特征是反复发作，发病年龄、类型和频率不同，导致运动、感觉、认知、精神或自主神经紊乱。自1995年首次发现单基因突变以来，人们提出遗传因素在癫痫发病机制中起重要作用。在特发性癫痫中发现的基因编码离子通道或神经递质受体蛋白，而以癫痫为主要特征的综合征是由参与皮层发育、线粒体功能和细胞代谢等功能的基因引起的。这些单基因癫痫致病基因的鉴定为癫痫的发病机制提供了新的认识。虽然大多数已确定的基因突变表现为单基因遗传，但大多数特发性癫痫是复杂的遗传疾病，表现为多基因或少基因遗传。本文综述了近年来癫痫发病机制的遗传和分子研究进展，重点介绍了单基因癫痫致病基因，包括电压门控通道（Na+、K+、Ca2+、Cl-和HCN）、配体门控通道（烟碱乙酰胆碱和GABA(A)受体）、非离子通道基因以及线粒体DNA基因。这些进展提高了我们对复杂神经系统疾病的理解。
Epilepsy is one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system. The clinical features of this disorder are recurrent seizures, difference in age onset, type, and frequency, leading to motor, sensory, cognitive, psychic, or autonomic disturbances. Since the discovery of the first monogenic gene mutation in 1995, it is proposed that genetic factor plays an important role in the mechanism of epilepsy. Genes discovered in idiopathic epilepsies encode for ion channel or neurotransmitter receptor proteins, whereas syndromes with epilepsy as a main feature are caused by genes that are involved in functions such as cortical development, mitochondrial function, and cell metabolism. The identification of these monogenic epilepsy-causing genes provides new insight into the pathogenesis of epilepsies. Although most of the identified gene mutations present a monogenic inheritance, most of idiopathic epilepsies are complex genetic diseases exhibiting a polygenic or oligogenic inheritance. This article reviews recent genetic and molecular progresses in exploring the pathogenesis of epilepsy, with special emphasis on monogenic epilepsy-causing genes, including voltage-gated channels (Na+, K+, Ca2+, Cl-, and HCN), ligand-gated channels (nicotinic acetylcholine and GABA(A) receptors), non-ion channel genes as well as the mitochondrial DNA genes. These progresses have improved our understanding of the complex neurological disorder.