Gap Activity TOward Rags 1 variants in Chinese people with sporadic drug-resistant focal epilepsy
Gap Activity TOward Rags 1 variants in Chinese people with sporadic drug-resistant focal epilepsy
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中国散发性耐药局灶性癫痫人群中 TOward Rags 1 变异的缺口活性
DOI：
10.1111/ane.13046
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发表时间：
2019
影响因子：
3.5
通讯作者：
Zhou Dong
中科院分区：
文献类型：
--
作者：
Xiong Weixi;Tang Lin;Lu Lu;Zhang Le;Xiao Yingfeng;Zhou Dong
gator1 （Gap Activity TOward Rags 1）由三个不同的亚基组成，DEPDC5(DEP结构域含蛋白5),NPRL2（氮渗透酶调节样2）和nprl3（氮渗透酶调节样3），这三个基因的变异在家族局灶性癫痫中大多被报道。然而，对散发的局灶性耐药癫痫患者进行的研究很少。在这项研究中，我们旨在确定散发耐药局灶性癫痫患者中inDEPDC5、nprl2和nprl3变异的频率。材料与方法133例中国散发性耐药局灶性癫痫患者纳入研究。对depdc5、nprl2和nprl3进行靶向测序，平均覆盖深度为2500x。结果193例散发性局灶性癫痫患者中位年龄为24.6岁，发病中位年龄为13.99岁，其中130例有明显的结构性病变。在1例（0.52%）海马硬化症患者中发现了一种可能致病的depdc5错义变体c.2984G>A, p.Arg995His，以及一种意义未知的变体DEPDC5c。20A>G, p.Tyr7Cys，在2例海马硬化患者中发现（1.04%）。结论在中国散发性耐药局灶性癫痫患者中，depdc5可能比annprl2或nprl3更重要。今后的研究重点应放在雷帕霉素机制靶点（mTOR）参与散发性癫痫发生的机制上。
ObjectivesGATOR1(Gap Activity TOward Rags 1) is composed of three different subunits,DEPDC5(DEP domain‐containing protein 5),NPRL2(nitrogen permease regulator‐like 2) andNPRL3(nitrogen permease regulator‐like 3), and variants in these three genes have mostly been reported in familial focal epilepsy. However, very few studies have been carried out on sporadic drug‐resistant focal epilepsy patients. In this study, we aimed to identify the frequency of variants inDEPDC5,NPRL2andNPRL3in patients with sporadic drug‐resistant focal epilepsy.Materials & methodsOne hundred and ninety‐three Chinese people with sporadic drug‐resistant focal epilepsy were enrolled in the study. Targeted sequencing ofDEPDC5,NPRL2andNPRL3was applied at an average coverage depth of 2500×.ResultsIn the 193 patients with sporadic focal epilepsy included in this study, the median age was 24.6 years with a median age at onset of 13.99 years, and 130 of these patients had identifiable structural lesions. One possibly pathogenic missense variant ofDEPDC5, c.2984G>A, p.Arg995His, was found in one patient (0.52%) with hippocampal sclerosis, and one variant of unknown significance,DEPDC5c.20A>G, p.Tyr7Cys, was found in two patients with hippocampal sclerosis (1.04%).ConclusionsOur findings suggested thatDEPDC5might be of more importance thanNPRL2orNPRL3in Chinese epilepsy patients with sporadic drug‐resistant focal epilepsy. Future research should focus on the mechanism by which the mechanistic target of rapamycin (mTOR) is involved in epileptogenesis in sporadic epilepsy.