Abstract：
DEPDC5-related epilepsy, caused by pathogenic germline variants(with or without additional somatic variants in the brain) of DEPDC5 (Dishevelled, Egl-10 and Pleckstrin domain-containing protein 5) gene, is a newly discovered predominantly focal epilepsy linked to enhanced mTORC1 pathway. DEPDC5-related epilepsy includes several familial epilepsy syndromes, including familial focal epilepsy with variable foci (FFEVF) and rare sporadic nonlesional focal epilepsy. DEPDC5 has been identified as one of the more common epilepsy genes linked to infantile spasms and sudden unexpected death (SUDEP). Although intelligence usually is unaffected in DEPDC5-related epilepsy, some people have been diagnosed with intellectual disabilities, autism spectrum disorder, and other psychiatric problems. DEPDC5 variants have also been found in 20% of individuals with various brain abnormalities, challenging the traditional distinction between lesional and nonlesional epilepsies. The most exciting development of DEPDC5 variants is the possibility of precision therapeutics using mTOR inhibitors, as evidenced with phenotypic rescue in many animal models. However, more research is needed to better understand the functional impact of diverse (particularly missense or splice-region) variants, the specific involvement of DEPDC5 in epileptogenesis, and the creation and utilization of precision therapies in humans. Precision treatments for DEPDC5-related epilepsy will benefit not only a small number of people with the condition, but they will also pave the way for new therapeutic approaches in epilepsy (including acquired epilepsies in which mTORC1 activation occurs, for example, post-traumatic epilepsy) and other neurological disorders involving a dysfunctional mTOR pathway.
摘要：
DEPDC5相关癫痫,由DEPDC5的致病性种系变异（在大脑中有或没有其他体细胞变异）引起的（Dishevelled，Egl-10和含Pleckstrin结构域的蛋白5)基因，是一种新发现的主要与mTORC1通路增强相关的局灶性癫痫。DEPDC5相关的癫痫包括几种家族性癫痫综合征，包括具有可变病灶的家族性局灶性癫痫（FFEVF）和罕见的散发性非病灶性局灶性癫痫。DEPDC5已被确定为与婴儿痉挛和猝死（SUDEP）相关的更常见的癫痫基因之一。尽管在DEPDC5相关的癫痫中智力通常不受影响，有些人被诊断患有智力障碍，自闭症谱系障碍，和其他精神问题。DEPDC5变体也被发现在20％的个体与各种大脑异常，挑战传统的区分病灶和非病灶性癫痫。DEPDC5变体最令人兴奋的发展是使用mTOR抑制剂进行精确治疗的可能性，正如在许多动物模型中的表型拯救所证明的那样。然而,需要更多的研究来更好地了解不同（特别是错义或剪接区域）变体的功能影响，DEPDC5在癫痫发生中的具体参与，以及精确疗法在人类中的创造和利用。DEPDC5相关癫痫的精准治疗不仅会使少数患者受益，但它们也将为癫痫的新治疗方法铺平道路（包括发生mTORC1激活的获得性癫痫，例如,创伤后癫痫)和其他涉及功能失调的mTOR通路的神经系统疾病。
