A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2

Epilepsia. 2014 Feb;55(2):370-8. doi: 10.1111/epi.12502. Epub 2013 Dec 24.


Objectives: Rolandic epilepsies (REs) represent the most frequent epilepsy in childhood. Patients may experience cognitive, speech, language, reading, and behavioral issues. The genetic origin of REs has long been debated. The participation of rare copy number variations (CNVs) in the pathophysiology of various human epilepsies has been increasingly recognized. However, no systematic search for microdeletions or microduplications has been reported in RE so far.

Methods: Array comparative genomic hybridization (aCGH) and quantitative polymerase chain reaction (qPCR) were used to analyze the genomic status of a series of 47 unrelated RE patients who displayed various types of electroclinical manifestations.

Results: Thirty rare CNVs were detected in 21 RE patients. Two CNVs were de novo, 12 were inherited, and 16 were of unknown inheritance. Each CNV was unique to one given patient, except for a 16p11.2 duplication found in two patients. The CNVs of highest interest comprised or disrupted strong candidate or confirmed genes for epileptic and other neurodevelopmental disorders, including BRWD3, GRIN2A, KCNC3, PRKCE, PRRT2, SHANK1, and TSPAN7.

Significance: Patients with REs showed rare microdeletions and microduplications with high frequency and heterogeneity. Whereas only a subset of all genomic alterations found here may actually participate in the phenotype, the novel de novo events as well as several inherited CNVs contain or disrupt genes, some of which are likely to influence the emergence, the presentation, or the comorbidity of RE. The future screening of cohorts of larger size will help in detecting more de novo or recurrent events and in appreciating the possible enrichment of specific CNVs in patients with RE.

Keywords: 16p11.2 duplication; Array-CGH; GRIN2A; PRRT2; Rolandic epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Copy Number Variations / genetics
  • Epilepsy, Rolandic / diagnosis*
  • Epilepsy, Rolandic / genetics*
  • Female
  • Genetic Association Studies / methods*
  • Genetic Heterogeneity
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Receptors, N-Methyl-D-Aspartate / genetics*


  • Membrane Proteins
  • Nerve Tissue Proteins
  • PRRT2 protein, human
  • Receptors, N-Methyl-D-Aspartate
  • N-methyl D-aspartate receptor subtype 2A