Retrospective investigation of genetic etiology in pediatric epilepsy patients based on targeted next generation sequence analysis datas

Aim: Epilepsy is a multifactorial disease which affects 0.5% to 1% of children and is characterized with recurrent seizures. Although various factors are shown to be responsible in its etiology; genetic factors are involved in 40-50% of the etiology. Numerous molecular changes have been identified in the etiology in patients with epilepsy by means of recent advances in NGS technologies. This paved the way for personalized treatments by determining the exact etiology in epilepsy patients. In this thesis study, it was aimed to examine the effect of the epilepsy panel on clinical decision making and to determine the diagnostic value of the NGS system in pediatric epilepsy patients by retrospectively examining the data of the targeted NGS panel in pediatric patients with epilepsy. Material and Method: In this thesis study, 107 pediatric patients(0-18 years old), who were evaluated with the diagnosis of epilepsy in İnönü University Faculty of Medicine Medical Genetics Polyclinic between 2018-2021 and to whom targeted NGS analyzes was performed for diagnosis, were included. The study included variants that are pathogenic, LP, and of VUS. The diagnostic value of the NGS panel was calculated with the obtained causal variants. Findings: In the study, 74 variants were detected, of which 20 were pathogenic, 5 were LP, and 49 were of VUS. After reanalysis of VUS variants, the ACMG classification of 36 variants, including 15 benign, 15 likely benign, 5 LP, and 1 pathogenic, were redefined. Accordingly, a total of 31 P, LP and 13 VUS variants were detected. In this study, the predictive value of the NGS panel containing 110 epilepsy genes was calculated as 28%. Conclusion: In our study, the diagnostic value of targeted NGS analysis in epilepsy patients was determined in accordance with current literature data. Identification of genetic etiology with NGS in cases allows prediction of prognosis and selection of appropriate treatment. Keywords: Epilepsy, gene panel, next generation sequencing