Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes

PLoS One. 2018 Jun 20;13(6):e0199321. doi: 10.1371/journal.pone.0199321. eCollection 2018.

Abstract

Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asian People / genetics*
  • Base Sequence
  • Case-Control Studies
  • Epilepsy, Generalized / genetics*
  • Family
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Humans
  • Male
  • Mutation / genetics
  • Pedigree
  • Syndrome
  • Young Adult

Grants and funding

This research was supported by an EMBRI Grant (2016EMBRISN0001) from the Eulji University and a grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF-2017R1D1A1B03034685) from the Ministry of Education.