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
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.
