遗传性癫痫伴热性惊厥附加症(Genetic epilepsy with febrile seizures plus,GEFS+)是一种新型遗传性癫痫综合征,具有明显的家族遗传史。临床表现常为热性惊厥,其次是热性惊厥附加症及伴或不伴失神发作、局灶性发作及全身强直-阵挛性发...遗传性癫痫伴热性惊厥附加症(Genetic epilepsy with febrile seizures plus,GEFS+)是一种新型遗传性癫痫综合征,具有明显的家族遗传史。临床表现常为热性惊厥,其次是热性惊厥附加症及伴或不伴失神发作、局灶性发作及全身强直-阵挛性发作等。利用聚合酶连反应、外显子测序、单核苷酸多态性分析等技术研究发现,其发生主要与γ-氨基丁酸A型受体的γ2亚基(Gamma aminobutyric acid type A receptor gamma 2 subunit,GABRG2)基因突变有关,但其发病机制仍未阐明。GABRG2突变类型主要有错义突变、无义突变、移码突变、点突变及剪接体位点突变等。其所有类型的突变均会降低细胞膜上相关离子通道的功能,但引起功能障碍的程度和机制并不相同,这可能是致痫的主要机制。文章将重点综述近年来研究发现的该基因突变类型与GEFS+相关性,为辅助临床精确诊断、抗癫痫治疗策略及新药开发具有重要意义。展开更多
Background:Emerging evidence has implied that the GABRG2 gene play a role in the mechanism of febrile seizure(FS),however,the relationship between GABRG2 rs211037 polymorphism and the risk of FS remains controversial....Background:Emerging evidence has implied that the GABRG2 gene play a role in the mechanism of febrile seizure(FS),however,the relationship between GABRG2 rs211037 polymorphism and the risk of FS remains controversial.This meta-analysis was conducted to investigate the relationship of GABRG2 rs211037 polymorphism with the susceptibility to FS.Methods:MEDLINE,Embase,Cochrane Library and CNKI databases were searched(until April 6,2019)for eligible studies on the relationship between GABRG2 rs211037 polymorphism and FS.We calculated the odds ratios(ORs)by a fixed or random model with the STATA 15.0 software.Subgroup analyses for the ethnicity,the source of the control,and age and sex matching of controls were conducted.Results:A total of 8 studies consisting of 775 FS patients and 5162 controls were included in this study.Based on the overall data,he GABRG2 rs211037 polymorphism was not significantly associated with the risk of FS(TT+CT vs CC:OR=0.95,95%CI 0.64–1.41,P=0.80).Notably,the GABRG2 rs211037 variant was significantly associated with decreased risk of FS in Asian populations(TT vs CT+CC:OR=0.63,95%CI 0.45–0.88,P=0.006),but increased risk in Caucasian populations(CT vs CC:OR=1.56,95%CI 1.14–2.15,P=0.006).Significant associations were also detected when healthy controls out of the whole controls were employed for comparison(TT vs CT+CC:OR=0.59,95%CI 0.45–0.77,P<0.001)and when data from studies with age-and sex-matched controls were used(TT+CT vs CC:OR=0.60,95%CI 0.43–0.86,P=0.001).Conclusion:The GABRG2 rs211037 polymorphism may decrease the risk of FS in Asian populations,while increasing the risk in Caucasian populations.Further well-designed studies with large sample sizes are essential to verify the conclusions in other ethnicities.展开更多
Background:We performed this meta-analysis to investigate the association between GABRG2 rs211037polymorphism and the risk for idiopathic generalized epilepsies(IGEs).Methods:Medline,Embase,Cochrane Library and Chines...Background:We performed this meta-analysis to investigate the association between GABRG2 rs211037polymorphism and the risk for idiopathic generalized epilepsies(IGEs).Methods:Medline,Embase,Cochrane Library and Chinese National Knowledge Infrastructure(CNKI)databases were searched for eligible studies(until May 5,2020)on the association between GABRG2 rs211037 polymorphism and IGE.The odds ratios were calculated using a fixed or random model in STATA 15.0 software.Subgroup analyses for ethnicity,age,source of controls,type of seizure syndrome and therapeutic responses were conducted.Results:We found no significant associations between GABRG2 rs211037 polymorphism and the susceptibility to IGEs.In addition,no significant association was detected between GABRG2 rs211037 polymorphism and drug resistance in IGE patients.The results did not change after stratification by Asian population,healthy controls,children,juvenile myoclonic epilepsy,and childhood absence epilepsy.Conclusion:The current studies indicated that the GABRG2 rs211037 polymorphism was not related to susceptibility or drug resistance of IGE.Further well-designed studies are needed to verify the results.展开更多
文摘目的探讨Gabrg2-CKO小鼠作为遗传性癫痫伴热性惊厥附加综合征(GEFS+)模型在静息状态下的全脑功能连接特征,并评估其在神经功能网络上的异常变化。方法采用超声功能成像(f US)技术对Gabrg2-CKO小鼠和C57BL/6J小鼠进行轻度镇静下全脑f US 3D扫描。基于Allen脑图谱,提取200多个感兴趣脑区(ROI)的脑血容量(CBV)信号,计算功能连接矩阵并进行组间差异分析。结果与C57BL/6J对照组小鼠相比,Gabrg2-CKO小鼠存在神经功能网络重组(P<0.001),前扣带回多个亚区之间的功能连接减弱(P<0.05);体感皮层与压后皮层及苍白球的功能连接增强(P<0.05);苍白球与海马CA3区的功能连接减弱(P<0.001);脑室系统与体感皮层/丘脑的双向功能连接异常(P<0.001);丘脑核间及丘脑与皮层的功能连接增强(P<0.05)。结论Gabrg2-CKO小鼠作为GEFS+模型在静息状态下表现出显著的全脑功能连接异常,Gabrg2基因缺失可能是导致神经功能网络紊乱的原因。
文摘遗传性癫痫伴热性惊厥附加症(Genetic epilepsy with febrile seizures plus,GEFS+)是一种新型遗传性癫痫综合征,具有明显的家族遗传史。临床表现常为热性惊厥,其次是热性惊厥附加症及伴或不伴失神发作、局灶性发作及全身强直-阵挛性发作等。利用聚合酶连反应、外显子测序、单核苷酸多态性分析等技术研究发现,其发生主要与γ-氨基丁酸A型受体的γ2亚基(Gamma aminobutyric acid type A receptor gamma 2 subunit,GABRG2)基因突变有关,但其发病机制仍未阐明。GABRG2突变类型主要有错义突变、无义突变、移码突变、点突变及剪接体位点突变等。其所有类型的突变均会降低细胞膜上相关离子通道的功能,但引起功能障碍的程度和机制并不相同,这可能是致痫的主要机制。文章将重点综述近年来研究发现的该基因突变类型与GEFS+相关性,为辅助临床精确诊断、抗癫痫治疗策略及新药开发具有重要意义。
基金supported by the National Natural Science Foundation of Shandong,China(ZR2019PH040)the National Natural Science Foundation of China(81901321).
文摘Background:Emerging evidence has implied that the GABRG2 gene play a role in the mechanism of febrile seizure(FS),however,the relationship between GABRG2 rs211037 polymorphism and the risk of FS remains controversial.This meta-analysis was conducted to investigate the relationship of GABRG2 rs211037 polymorphism with the susceptibility to FS.Methods:MEDLINE,Embase,Cochrane Library and CNKI databases were searched(until April 6,2019)for eligible studies on the relationship between GABRG2 rs211037 polymorphism and FS.We calculated the odds ratios(ORs)by a fixed or random model with the STATA 15.0 software.Subgroup analyses for the ethnicity,the source of the control,and age and sex matching of controls were conducted.Results:A total of 8 studies consisting of 775 FS patients and 5162 controls were included in this study.Based on the overall data,he GABRG2 rs211037 polymorphism was not significantly associated with the risk of FS(TT+CT vs CC:OR=0.95,95%CI 0.64–1.41,P=0.80).Notably,the GABRG2 rs211037 variant was significantly associated with decreased risk of FS in Asian populations(TT vs CT+CC:OR=0.63,95%CI 0.45–0.88,P=0.006),but increased risk in Caucasian populations(CT vs CC:OR=1.56,95%CI 1.14–2.15,P=0.006).Significant associations were also detected when healthy controls out of the whole controls were employed for comparison(TT vs CT+CC:OR=0.59,95%CI 0.45–0.77,P<0.001)and when data from studies with age-and sex-matched controls were used(TT+CT vs CC:OR=0.60,95%CI 0.43–0.86,P=0.001).Conclusion:The GABRG2 rs211037 polymorphism may decrease the risk of FS in Asian populations,while increasing the risk in Caucasian populations.Further well-designed studies with large sample sizes are essential to verify the conclusions in other ethnicities.
基金supported by the National Natural Science Foundation of Shandong,China(item number ZR2019PH040)the National Natural Science Foundation of China(item number 81901321).
文摘Background:We performed this meta-analysis to investigate the association between GABRG2 rs211037polymorphism and the risk for idiopathic generalized epilepsies(IGEs).Methods:Medline,Embase,Cochrane Library and Chinese National Knowledge Infrastructure(CNKI)databases were searched for eligible studies(until May 5,2020)on the association between GABRG2 rs211037 polymorphism and IGE.The odds ratios were calculated using a fixed or random model in STATA 15.0 software.Subgroup analyses for ethnicity,age,source of controls,type of seizure syndrome and therapeutic responses were conducted.Results:We found no significant associations between GABRG2 rs211037 polymorphism and the susceptibility to IGEs.In addition,no significant association was detected between GABRG2 rs211037 polymorphism and drug resistance in IGE patients.The results did not change after stratification by Asian population,healthy controls,children,juvenile myoclonic epilepsy,and childhood absence epilepsy.Conclusion:The current studies indicated that the GABRG2 rs211037 polymorphism was not related to susceptibility or drug resistance of IGE.Further well-designed studies are needed to verify the results.
