DEPDC5基因相关癫痫研究进展

Research progress of dishevelled, Egl-10, and pleckstrin domain-containing protein 5 gene-related epilepsy

雷帕霉素靶蛋白(mTOR)通路在多种神经系统疾病,特别是癫痫的发生中具有重要作用。DEPDC5(dishevelled, Egl-10, and pleckstrin domain-containing protein 5)基因相关癫痫是近年来新发现的一类mTOR通路相关基因突变疾病。DEPDC5基因突变的临床表型多样,其突变已在多种遗传性局灶性癫痫、局灶性脑皮质发育不良Ⅱ型以及散发性局灶性癫痫病例中发现。该病的发生机制尚未明确,DEPDC5功能缺失继发的mTOR通路过度活化可能是主要致痫机制。DEPDC5基因相关癫痫与其他具有mTOR通路过度活化特征的神经系统发育性疾病共同构成了mTOR通路疾病谱。

Mechanistic target of rapamycin (mTOR) pathway has been associated to various neurological diseases, including epilepsy. As a newly discovered mTOR pathway disease, DEPDC5 (dishevelled, Egl-10, and pleckstrin domain-containing protein 5) gene related epilepsy covers a range of clinical phenotypes. Mutations of DEPDC5 gene have been detected in genetic focal epilepsies, focal cortical dysplasia type Ⅱ, and sporadic focal epilepsy cases. It has been reported that hyperactivation of mTOR signaling due to the loss of function of DEPDC5 contributes to epileptogenesis, however more detailed mechanisms remain to be elucidated. DEPDC5 gene-related epilepsy together with other neurodevelopmental diseases characterized by hyperactivation of mTOR signaling has formed a disease spectrum named mTORopathies.