AIM: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients. METHODS: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed. RESULTS: Out of 175 patients, described pathogenic variants or novel variants with clear pathogenic impact were identified in 30 patients (17.14%). Genotype-phenotype correlations and parental DNA analysis were performed, and genetic diagnosis was confirmed on the basis of the results in another 16 out of 175 patients (9.14%). The diagnostic yield of our study increased from 30 to 46 patients (by 53.33%) by the precise genotype-phenotype correlation. INTERPRETATION: We emphasize a complex genotype-phenotype correlation and a multidisciplinary approach in evaluating the results of the NGS epilepsy gene panel, which enables the most accurate genetic diagnosis and correct interpretation of results.

Brno Epilepsy Center 1st Department of Neurology St Anne's University Hospital and Medical Faculty of Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic

Centre of Molecular Biology and Genetics Internal Haematology and Oncology Clinic Masaryk University and University Hospital Brno Czech Republic

Department of Pediatric Neurology Faculty of Medicine Masaryk University and University Hospital Brno Brno Epilepsy Centre Czech Republic

Institute of Medical Genetics and Genomics Faculty of Medicine Masaryk University and University Hospital Brno Czech Republic

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$a Horák, Ondřej $u Department of Pediatric Neurology, Faculty of Medicine, Masaryk University and University Hospital Brno, Brno Epilepsy Centre, Czech Republic

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$a Next-generation sequencing in children with epilepsy: The importance of precise genotype-phenotype correlation / $c O. Horák, M. Burešová, S. Kolář, K. Španělová, B. Jeřábková, R. Gaillyová, K. Česká, K. Réblová, J. Šoukalová, J. Zídková, L. Fajkusová, H. Ošlejšková, I. Rektor, P. Danhofer

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$a AIM: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients. METHODS: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed. RESULTS: Out of 175 patients, described pathogenic variants or novel variants with clear pathogenic impact were identified in 30 patients (17.14%). Genotype-phenotype correlations and parental DNA analysis were performed, and genetic diagnosis was confirmed on the basis of the results in another 16 out of 175 patients (9.14%). The diagnostic yield of our study increased from 30 to 46 patients (by 53.33%) by the precise genotype-phenotype correlation. INTERPRETATION: We emphasize a complex genotype-phenotype correlation and a multidisciplinary approach in evaluating the results of the NGS epilepsy gene panel, which enables the most accurate genetic diagnosis and correct interpretation of results.

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