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Determining the best candidates for next‐generation sequencing‐based gene panel for evaluation of early‐onset epilepsy

Year: 2020
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Genetic testing is an emerging diagnostic approach in early-onset epilepsy. Identification of the heterogeneous genetic causes of epilepsy may mitigate unnecessary evaluations and allow more accurate diagnosis and therapy. We aimed to uncover genetic causes of early-onset epilepsy using next-generation sequencing (NGS) to elucidate the diagnostic candidates and evaluate the diagnostic yield of targeted gene panel testing. METHODS: We evaluated 116 patients with early-onset epilepsy developed before 2 years old and normal brain imaging using a NGS-based targeted gene panel. Variants were classified according to their pathogenicity, and the diagnostic yield of the targeted genes and associated clinical factors were determined. RESULTS: We detected 40 disease-causing variants with diagnostic yield of 34.5% (19 pathogenic, 21 likely pathogenic). Twelve variants were novel. The most commonly detected genes were SCN1A, associated with Dravet syndrome, and PRRT2, associated with benign familial infantile epilepsy. Other variants were identified in ARX, SCN2A, KCNQ2, PCDH19, STXBP1, DEPDC5, and SCN8A. The age of seizure onset and family history were associated with disease-causing variants. CONCLUSION: Next-generation sequencing-based targeted testing is an effective diagnostic test, with 30%-40% comparable diagnostic yield. Patients with earlier seizure onset and family history of epilepsy were the best candidates for testing. For pediatric patients with early-onset epilepsy, genetic diagnosis is important for accurate prognosis and treatment.
DOI: 10.1002/mgg3.1376
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,200
OpenAlex ID: W3040254839
FWCI: 2.549
Cites: 46
Cited by: 26
Related to: 10