Gene Expression Analysis And Clinical Analysis Of 95 Cases Of Children With Epilepsy

BackgroundEpilepsy is one of the most common diseases in the pediatric nervous system.Its etiology is complex and diverse,including heredity,metabolic,structural,immunological,infectious,and unknown causes,etc.Among them,there are many multiple etiologies repeated crossing which resulted in difficulties in clinical diagnosis and treatment.Genetic factors is always a research hotspot in the cause of epilepsy.With the rapid development of medical technology,the emergence of the two generation high throughput gene sequencing platform provide an important basis for the study of the cause of epilepsy.It not only study on the related factors influencing epilepsy from genomics,transcriptomics,proteomics epigenetic study group and other multiple groups,but also have a better understanding of the occurrence of epilepsy and the association between development and prognosis through the confluence analysis of high-throughput analysis for various levels of learning data,which will provide more research directions and ideas for more and more popular accurate medical research,and provide more possibilities for further understanding the etiology of epilepsy,early diagnosis,targeting and individual treatment.ObjectiveWe have summarized the clinical features of some refractory or some genetically related children with epilepsy in clinical diagnosis and treatment and carried out the two generation of high-throughput gene sequencing and generation of verification on them.To analyze the relationship between mutant genes and epilepsy,to understand the genetic pattern of children and to look for possible pathogenic or disease causing mutation.MethodsEstablish a complete pedigree database for 95 children and their parents diagnosed in pediatric neurology clinic in our hospital,and carry out gene testing on them by using two generation high-throughput gene sequencing.Then we have the analysis on the basis of clinical features and gene type in children.Results1.Clinical and prognosisRefractory or genetically related children had a smaller age range and had a variety of clinical features.Most of them(47/95,49%)needed two or more drugs for treatment;28% of them was controlled which was about 27cases;21% of them was effective which was about 20 cases;33% of them was marked which was about 32 cases;12% of them was of no effect which was about 12 cases;4% of them was missed which was about 4 cases.A small number of children(18/95,19%)had poor prognosis and accompanied with exercise and mental retardation.2.Genotype detection results2.1 Pathogenic genes of total 16 cases(17%)were cleared except 1 case of CASK,the others were all the new mutation.10 cases of them were shear mutation,5 of them were missense mutation and 1 case of them was missense mutation.There were about 5 cases of Dravet syndrome and the mutated genes were all SCNIA.There was 1 cases of infantile spasms and the mutated gene was BRAF.There was 1 cases of TSC1 and TSC2 and the the clinical diagnosis was tuberous sclerosis.The remaining 7 mutant genes were 3 cases of SCN1A?1case of STS?2 cases of FLNA?and 1 case of KCNQ2.2.2 There were about a total of 21 cases(22%)of possible pathogenic gene in which there were 3 cases of infant patients with infantile spasms whose mutated genes were DIAPH3(combined with RNF213)? ABCC8(combined with RANBP2)and ASPM.There were 2 cases of shear mutation.The rest of the pathogenic gene were 1 case of CLCN2 ? 3 cases of DMD ? 1 case of SMN1 ? 2 cases of KCNT1 ? 1 case ofKANK1?1 case of SYNE1?1 case of SRPX2?1 case of MBD5?1 case of EFHC2?1case of SPTAN1?1 case of GRIA1?1 case of DIAPH3?1 case of GRIN3B?1 case of SV2 A and 1 case of KACNF1.4 cases of them previously reported that they associated with epilepsy.2.3 There were about a total of 30 cases(31%)of non pathogenic gene and the mutated genes were 1 case of SMN2 ? 1 case of GRIA1 ? 1 case of PAH ? 4 cases of SCN3 A ? 1 case of COL6A3 ? 1 case of FOXP1 ? 1 case of TREX1 ? 3 cases of KCNQ4?1 case of SLC3A1?1 case of PRF1?1 case of CPT1A?1 case of PSEN2?1case of PSEN2 ? 6 cases of SCN9 A ? 1 case of ASPM ? 1 case of MECP2 ? 1 case of RNF213?1 case of KTNF?1 case of OTC?1 case of ANKR and 3 of them were shear mutation.2.4 A total of 28 cases were not detected mutated gene which was about 29%.Conclusion1.We have found two new virulence gene of CASK and BRAF which had few reports in China and expanded the number of genes associated with neural development and epilepsy associated genes.2.The clinical characteristics of SCNIA gene mutations in Dravet syndrome were more serious which include earlier onset,frequent seizures and poor treatment effect.3.Most children with specific causative genes required the combined use of two or more drugs,which has difficulties in treatment.