目的对DEPDC5基因rs1012068和rs5998152单核苷酸多态性与肝细胞癌(HCC)易感性的关系进行系统评价。方法截至2022年10月31日,联合应用PubMed、Embase、Scopus、Web of Science和中国知网(CNKI)数据库,全面检索关于rs1012068、rs5998152与...目的对DEPDC5基因rs1012068和rs5998152单核苷酸多态性与肝细胞癌(HCC)易感性的关系进行系统评价。方法截至2022年10月31日,联合应用PubMed、Embase、Scopus、Web of Science和中国知网(CNKI)数据库,全面检索关于rs1012068、rs5998152与HCC易感性关系的研究。计算五种遗传模式的效应指标OR值及95%CI,采用RevMan5.3软件进行meta分析。结果本研究共纳入12篇文献,关于rs1012068位点的11篇文献,共纳入HCC患者2609例,对照者8171例;关于rs5998152位点的3篇文献,共纳入HCC患者411例,对照者1448例。Meta分析结果显示,rs1012068位点的5种遗传学模式中,等位基因模式(G vs T:P=0.02)、显性模式(GG+TG vs TT:P=0.01)和杂合子模式(TG vs TT:P=0.009)在病例组和对照组之间比较,差异有统计学意义,在纯合子模式(GG vs TT:P=0.05)和隐性模式(GG vs TG+TT:P=0.08)中,rs1012068基因多态性与HCC易感性无相关性。rs5998152位点的5种遗传学模式中,等位基因模式(C vs T:P=0.03)、显性模式(CC+TC vs TT:P=0.001)和杂合子模式(TC vs TT:P<0.00001)在病例组和对照组之间比较,差异有统计学意义,在隐性模式(CC vs TC+TT:P=0.31)和纯合子模式(CC vs TT:P=0.09)中,rs5998152基因多态性与HCC易感性无相关性。结论rs1012068位点在等位基因模式和显性基因模式中,与HCC易感性之间存在相关性,是导致肿瘤发生的促进性遗传因素。rs5998152位点的等位基因模式、显性模式和杂合子模式可增加HCC的患病风险,其他模式未发现有相关性。展开更多
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...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。展开更多
Objective:DEPDC5 together with NPRL2 and NPRL3 forms the GATOR1 which plays an important role in the the mechanistic target of rapamycin(mTOR)pathway.Deregulation of mTOR signalling has been associated to various neur...Objective:DEPDC5 together with NPRL2 and NPRL3 forms the GATOR1 which plays an important role in the the mechanistic target of rapamycin(mTOR)pathway.Deregulation of mTOR signalling has been associated to various neurological conditions,including epilepsy.Variants in the gene encoding GATOR1 complex,especially in DEPDC5,have been implicated in the pathogensis of several focal epilepsies.While there was little report on the electroencephalogram(EEG)feature of DEPDC5 related epilepsy,we decided to investigate the specific EEG pattern and the prognosis of DEPDC5 related epilepsy.Methods:The records of 546 epilepsy patients with unknown causes who were admitted in Xijing Hospital and underwent whole exome sequencing(WES)from 2015 to 2019 were retrospectively reviewed.Finally,the clinical data of these 7 patients with DEPDC5 variants were collected in this study.We analyzed their clinical manifestations,EEG and magnetic resonance imaging(MRI).Results:Seven DEPDC5 variants,including six novel mutations,were identified in seven individuals with focal epilepsy.Among these patients,one had family history.Four showed specific interictal EEG patterns,periodic-like sharp waves or spike waves,were found in four patients.Five out of seven patients(71.4%)were well-controlled by anti-epilepsy drugs while two patients with sleep-related hypermotor epilepsy had either drug resistance or relapse of epilepsy.Conclusion:DEPDC5 variants were related to focal epilepsy in patients with or without family history.The EEG abnormalities of DEPDC5 related epilepsy were heterogeneous among different patients,while periodic-like sharp waves or spike waves might be the most characteristic interictal EEG pattern for DEPDC5 related epilepsies.In this study the prognosis of DEPDC5 related epilepsy was similar to other epilepsies.DEPDC5 variants may not predict the prognosis so far.展开更多
文摘目的对DEPDC5基因rs1012068和rs5998152单核苷酸多态性与肝细胞癌(HCC)易感性的关系进行系统评价。方法截至2022年10月31日,联合应用PubMed、Embase、Scopus、Web of Science和中国知网(CNKI)数据库,全面检索关于rs1012068、rs5998152与HCC易感性关系的研究。计算五种遗传模式的效应指标OR值及95%CI,采用RevMan5.3软件进行meta分析。结果本研究共纳入12篇文献,关于rs1012068位点的11篇文献,共纳入HCC患者2609例,对照者8171例;关于rs5998152位点的3篇文献,共纳入HCC患者411例,对照者1448例。Meta分析结果显示,rs1012068位点的5种遗传学模式中,等位基因模式(G vs T:P=0.02)、显性模式(GG+TG vs TT:P=0.01)和杂合子模式(TG vs TT:P=0.009)在病例组和对照组之间比较,差异有统计学意义,在纯合子模式(GG vs TT:P=0.05)和隐性模式(GG vs TG+TT:P=0.08)中,rs1012068基因多态性与HCC易感性无相关性。rs5998152位点的5种遗传学模式中,等位基因模式(C vs T:P=0.03)、显性模式(CC+TC vs TT:P=0.001)和杂合子模式(TC vs TT:P<0.00001)在病例组和对照组之间比较,差异有统计学意义,在隐性模式(CC vs TC+TT:P=0.31)和纯合子模式(CC vs TT:P=0.09)中,rs5998152基因多态性与HCC易感性无相关性。结论rs1012068位点在等位基因模式和显性基因模式中,与HCC易感性之间存在相关性,是导致肿瘤发生的促进性遗传因素。rs5998152位点的等位基因模式、显性模式和杂合子模式可增加HCC的患病风险,其他模式未发现有相关性。
文摘雷帕霉素靶蛋白(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。
基金National Key R&D Program of China,Precision medicine program——Cohort study on nervous system diseases under Grant2017YFC0907700(2017–2021).
文摘Objective:DEPDC5 together with NPRL2 and NPRL3 forms the GATOR1 which plays an important role in the the mechanistic target of rapamycin(mTOR)pathway.Deregulation of mTOR signalling has been associated to various neurological conditions,including epilepsy.Variants in the gene encoding GATOR1 complex,especially in DEPDC5,have been implicated in the pathogensis of several focal epilepsies.While there was little report on the electroencephalogram(EEG)feature of DEPDC5 related epilepsy,we decided to investigate the specific EEG pattern and the prognosis of DEPDC5 related epilepsy.Methods:The records of 546 epilepsy patients with unknown causes who were admitted in Xijing Hospital and underwent whole exome sequencing(WES)from 2015 to 2019 were retrospectively reviewed.Finally,the clinical data of these 7 patients with DEPDC5 variants were collected in this study.We analyzed their clinical manifestations,EEG and magnetic resonance imaging(MRI).Results:Seven DEPDC5 variants,including six novel mutations,were identified in seven individuals with focal epilepsy.Among these patients,one had family history.Four showed specific interictal EEG patterns,periodic-like sharp waves or spike waves,were found in four patients.Five out of seven patients(71.4%)were well-controlled by anti-epilepsy drugs while two patients with sleep-related hypermotor epilepsy had either drug resistance or relapse of epilepsy.Conclusion:DEPDC5 variants were related to focal epilepsy in patients with or without family history.The EEG abnormalities of DEPDC5 related epilepsy were heterogeneous among different patients,while periodic-like sharp waves or spike waves might be the most characteristic interictal EEG pattern for DEPDC5 related epilepsies.In this study the prognosis of DEPDC5 related epilepsy was similar to other epilepsies.DEPDC5 variants may not predict the prognosis so far.
