Gene Mutation Analysis Of Targeted Next Generation Sequencing In Patients With Unexplained Childhood Absence Epilepsy

Objects:Childhood absence epilepsy(CAE)is one type of common genetic generalized epilepsies.Recent studies have reported that more than half of epileptic children have a genetic basis.To date,though many genes related to CAE have been found,the etiology and pathogenesis remain unclear.Thus we used targeted next–generation sequencing in100 CAE children to find new susceptible genes and pathogenic mutations,providing the basis for the study of pathogenic mechanism of childhood absence epilepsy,also can be helpful to understand the possible pathogenesis of other types of genetic generalized epilepsies.In addition,it is also important to the diagnosis of hereditary epilepsy,treatment,genetic counseling and basic study.Methods:A total of 100 patients with unexplained CAE were recruited from Peking University First Hospital.We carried on the mutation screening using targeted next–generation sequencing(including 511 epilepsy gene panel)in 100 CAE patients to find possible pathogenic mutations.Then we verified the parental origin using the Sanger sequencing,analysized sequence conservation,analysized pathogenic mutations by gathering the results of biology genetics and clinical feature analyses,actually got pathogenic mutations.Results:We found 1131 variations in 100 CAE children,of which 3 missence mutations from3 CAE children were pathogenic mutations,including SCN1A(c.5,399T>A),SCN8A(c.2,371G>T)and CLCN2(c.481G>A),they were de novo.The functions of 3 proteins predicted by Polyphen2 were probably damaged.We got 2 variations from 1 CAE child,including GPR98(c.5815G>A)and GPR98(c.16252G>T).They were from mother andfather,respectively.The function of the former protein predicted by Polyphen2 was probably damaged,the latter was benign.According to the Human Gene Mutation Database(HGMD),these 5 mutations were located in highly conserved regions and were novel mutations.Conclusion:The genes SCN1 A,SCN8A,CLCN2 and GPR98 may be susceptible genes of childhood absence epilepsy.The discovery not only expands the disease spectrums of SCN1 A,SCN8A,CLCN2 and GPR98,but also finds possible pathogenic genes for childhood absence epilepsy.