Scheffer Ingrid E, Berkovic Samuel F
Department of Medicine (Neurology), The University of Melbourne, Epilepsy Research Institute, Austin & Repatriation Medical Centre, Australia.
Trends Pharmacol Sci. 2003 Aug;24(8):428-33. doi: 10.1016/S0165-6147(03)00194-9.
In recent years genetic discoveries have shown the central role of ion channels in the pathophysiology of idiopathic epilepsies. Uncommon epilepsy syndromes that have monogenic inheritance are associated with mutations in genes that encode subunits of voltage-gated and ligand-gated ion channels. For voltage-gated ion channels, mutations of Na(+), K(+) and Cl(-) channels are associated with forms of generalized epilepsy and infantile seizure syndromes. Ligand-gated ion channels, such as nicotinic acetylcholine receptors and GABA receptor subunits, are associated with specific syndromes of frontal and generalized epilepsies, respectively. Striking features are the variable epilepsy phenotypes that are associated with the known gene mutations and the genetic heterogeneity that underlies all known monogenic syndromes. Mutations in two genes that do not encode ion channels have been identified in the idiopathic human epilepsies. The heterogeneity of mutations described to date has precluded the development of simple diagnostic tests, but advances in the next few years are likely to have an impact on both the clinical diagnosis and the treatment of epilepsies.
近年来，遗传学研究发现表明离子通道在特发性癫痫的病理生理学中起着核心作用。具有单基因遗传的罕见癫痫综合征与编码电压门控离子通道和配体门控离子通道亚基的基因突变有关。对于电压门控离子通道，钠（Na⁺）、钾（K⁺）和氯（Cl⁻）通道的突变与全身性癫痫和婴儿惊厥综合征的多种形式相关。配体门控离子通道，如烟碱型乙酰胆碱受体和GABA受体亚基，分别与额叶癫痫和全身性癫痫的特定综合征相关。显著特征是与已知基因突变相关的可变癫痫表型以及所有已知单基因综合征背后的遗传异质性。在特发性人类癫痫中已鉴定出两个不编码离子通道的基因突变。迄今为止所描述的突变的异质性阻碍了简单诊断测试的开发，但未来几年的进展可能会对癫痫的临床诊断和治疗产生影响。
