Butler KM, et al. - Researchers carried out this study to ascertain the diagnostic yield of a clinical gene panel applied to an unselected cohort of epilepsy patients. In this study, 87 variants were identified in 30 different genes that could explain disease, of which 54% were not previously reported. They confirmed the utility of targeted gene panel analysis in epilepsy and underscored several factors to improve the yield of diagnostic genetic testing, including the critical need for clinical phenotype information and parental samples, microarray analysis for whole exon deletions and duplications, and frequent update of panels to incorporate new disease genes.

• The researchers retrospectively reviewed variant reports from 339 clinically-referred epilepsy patients screened using a 110-gene panel.
• They classified variants using ACMG guidelines.

• The researchers identified pathogenic or likely pathogenic variants in 62 individuals (18%) and potentially causative variants were identified in an additional 21 individuals (6%).
• In SCN1A (n = 15) and KCNQ2 (n = 10), causative and potentially causative variants were most frequently identified.
• Other genes in which disease-causing variants were identified in multiple individuals included CDKL5, SCN2A, SCN8A, SCN1B, STXBP1, TPP1, PCDH19, CACNA1A, GABRA1, GRIN2A, SLC2A1, and TSC2.
• As per the outcomes, 16 additional genes had variants identified in single individuals.