Research On The Circadian Rhythm Of The Seizures Of Genetic Epilepsy

Object:Analysis of the distribution of epileptic seizures in different genotypes,gene mutation patterns and gene-coding functional proteins during day,night and time periods,To obtain circadian rhythm of the seizures of Genetic Epilepsy characteristics.It provides new ideas for diagnosis,treatment and progonosis of genetic epilepsy.Methods:Collection of Pediatrics Neurology outpatient and ward of Zhujiang Hospital of Southern Medical University From January 1,2016 to December 31,2020,the clinical data of children who met the criteria of this study(basic clinical information,seizure time record and gene report,etc).Taking 355 seizure events as the study object,24 hours were divided into day/night,12 time periods,and the distribution characteristics of seizure frequency in day and night,12 time periods were analyzed.According to the different characteristics of the mutated genes,we divided into different genotypes,different gene mutation patterns,genes encoding different proteins to study the circadian characteristics of their seizures.Results:1.The total number of epileptic seizures was 355,including 20 male patients(43.48%),26 female patients(56.52%)and 7.72 per capita There were 11 species by genotype,SCN1A 20 patients,SCN8A 3 patients,SCN9A 2 patients,KCNTI 3 patients,KCNQ2 3 patients,CACNA1H 3 patients,GRIN2A 3 patients,PRRT2 Six patients,SCN2A 1 patients,KCNA2 1 patient,GRIN2D 1 patients.According to the American College of Medical Genetics and Genomics(ACMG)Classification of variants established:SCN1A genotype group:Categoryl-Pathogenicity:7,Category 2-Likely pathogenicity:12,Category 3-Uncertain significance:1;non SCN1A genotype group:Categoryl-Pathogenicity:6,Category 2-Likely pathogenicity:7,Category 3-Uncertain significance:13.Among the children included in the study,there were 34 missense mutations,3 missense mutations,1 splice site mutation,5 franeshift mutations,3 deletions and 1 repetition.Among the children included in the study,there were 36 coding voltage dependent ion channels,4 ligand-gated ion channels and 6 other proteins.2.We collected a total of 20 SCN1A gene mutations(170 seizures).The diurnal distribution of seizures SCN1A all gene mutations was not statistically significant(P=0.330),but we found that the time distribution of SCN1A gene mutations was statistically significant(PP=0.05).The peak period of seizures was 17:00-19:00.They were divided into missense mutation group and truncation mutation group according to different mutation forms of SCN1A gene.There was no significant distribution of missense mutation and truncation mutation in SCN1A gene(P>0.05),but there was significant difference in missense mutation time(P<0.05).3.There were 26 cases of non-SCN1A gene mutations,covering 10 genes,which were SCN8A,SCN9A、KCNT1、KCNQ2、CACNA1H,GRIN2A、PRRT2、SCN2A、KCNA2、GRIN2D.With the exception of he number of SCN2A、KCNA2 and GRIN2D cases≤1 was not statistically significant Epilepsy frequency distribution of the other non SCN1A genotypes was not statistically significant during day and night,at all time periods.Classified by gene mutation,The number of seizures with missense,nonsense and frameshift mutations was not statistically significant in day,night and time periods,duplicate form,missing form due to the number of cases ≤1 can not be statistically significant calculation.Epilepsy frequency of SCN8A、SCN9A、KCNT1、CACNA1H、GRIN2A、PRRT2 with gene mutation in the form of missense mutation was not statistically significant during day and night,The KCNA2、KCNQ2 of gene mutation in the form of missense mutation and the number of GRIN2D cases≤1 could not be calculated statistically.4.We are divided into gene en coding voltage-dependent ion channel proteome,gene en coding ligand-gated and other proteome according on gene en coding different functional proteins.Among the three groups,there was no difference in diurnal distribution of epileptic seizures,and there was no significant difference in the time distribution of gene en coding voltage.dependent ion channel proteome and other proteome(P>0.05).However,the time distribution of gene en coding ligand-gated ion channel proteome was statistically different(P<0.05),and the peak period of epileptic seizure was 13:00-15:00At the same time,this study found that there was significant difference in the composition ratio of diurnal frequency of gene en coding voltage dependent proteome(P<0.05),To further compare the two groups,The number of diurnal episodes of gene en coding the potassium channel proteome and gene en coding the calcium channel proteome are different,The potassium channel group had more seizures at night,while the calcium channel group had more seizures during the day.Conclusions:Epilepsy with SCN1A gene mutations is circadian rhythmic and related to its missense variation.GRIN2A and GRIN2D co-encoding seizures of ligand-gated ion channels also have circadian rhythm characteristics.The gene coding voltage depends on the circadian rhythm of different ion channel prote groups,the potassium channel group has more attacks at night,and the calcium channel group has more attacks during the day.