Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy

The epileptic encephalopathies (EEs) are a devastating group of epilepsies in which epileptic activity and seizures contribute to cognitive impairment or regression.1 Most EEs begin in infancy or early childhood and are associated with poor developmental outcome. Although the cause is unknown in the majority of cases, recent studies confirm that de novo mutations and copy number variants (CNVs) play an important role.2, 3 We recently reported exome sequencing data in 264 parent–proband trios with infantile spasms (n = 149) or Lennox–Gastaut syndrome (LGS; n = 115) without syndromic features or magnetic resonance imaging (MRI) abnormalities from the Epilepsy Phenome/Genome Project (EPGP) cohort, identifying likely pathogenic, de novo sequence changes in >10% of patients.2 Here we report results of copy number analysis derived from the exome data of this cohort and 85 additional patients to further elucidate the genetic architecture of these paradigmatic EEs. Our exome‐based CNV calling yields similar results to array‐based studies for confirmed, de novo, likely pathogenic CNVs.