1. Next-generation sequencing in children with epilepsy: The importance of precise genotype-phenotype correlation.
- Author
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Horák O, Burešová M, Kolář S, Španělová K, Jeřábková B, Gaillyová R, Česká K, Réblová K, Šoukalová J, Zídková J, Fajkusová L, Ošlejšková H, Rektor I, and Danhofer P
- Subjects
- Female, Genetic Association Studies, Genetic Testing methods, High-Throughput Nucleotide Sequencing methods, Humans, Male, Mutation, Phenotype, Retrospective Studies, DNA Copy Number Variations, Epilepsy diagnosis, Epilepsy genetics
- Abstract
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., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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