Deng Hao, Xiu Xiaofei, Song Zhi
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, Hunan, 410013, People's Republic of China,
Mol Neurobiol. 2014 Feb;49(1):352-67. doi: 10.1007/s12035-013-8523-6. Epub 2013 Aug 10.
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(+), Ca(2+), Cl(-), and HCN), ligand-gated channels (nicotinic acetylcholine and GABAA receptors), non-ion channel genes as well as the mitochondrial DNA genes. These progresses have improved our understanding of the complex neurological disorder.
癫痫是最常见的神经系统疾病之一，其特征是中枢神经系统出现异常电活动。该疾病的临床特征为反复发作的癫痫、发病年龄、类型和频率的差异，可导致运动、感觉、认知、精神或自主神经功能障碍。自1995年发现首个单基因基因突变以来，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则由参与皮质发育、线粒体功能和细胞代谢等功能的基因引起。这些单基因致癫痫基因的鉴定为癫痫的发病机制提供了新的见解。虽然大多数已鉴定出的基因突变呈现单基因遗传，但大多数特发性癫痫是表现为多基因或寡基因遗传的复杂遗传疾病。本文综述了探索癫痫发病机制方面最近的遗传和分子进展，特别强调单基因致癫痫基因，包括电压门控通道（Na⁺、K⁺、Ca²⁺、Cl⁻和HCN）、配体门控通道（烟碱型乙酰胆碱和GABAA受体）、非离子通道基因以及线粒体DNA基因。这些进展增进了我们对这种复杂神经系统疾病的理解。
