Abstracts

Rationale: Epilepsy is one of the most common neurological disorders, with a lifetime incidence of 3%. The epileptic encephalopathies are the most severe of all the epilepsies. Patients typically present with refractory epilepsy with multiple seizure types, cognitive arrest or regression, and have a poor prognosis. De novo mutations have been increasingly recognized as causative for these disorders, and mutations in over 30 genes have been described. Recently, de novo mutations in EEF1A2 were described in patients with intellectual disability and epilepsy.Methods: To define the role of this gene in epilepsy more broadly, we performed targeted resequencing of EEF1A2 in 683 patients with epileptic encephalopathy.Results: Overall, on average we sequenced 82% of the gene at a coverage of >50X across all samples. We identified four patients with likely pathogenic mutations, three patients had a recurrent Asp91Asn mutation and a fourth had a de novo Ala125Glu mutation. We review the phenotypes of these patients and contrast with those previously described.Conclusions: EEF1A2 encodes for the alpha subunit of the eukaryotic translation elongation factor that controls the delivery of tRNAs to the ribosome. The function of this protein reveals a novel biological mechanism for epileptogenesis and broadens our appreciation for the complex mechanisms that underpin epilepsy. Future functional studies will not only enhance our understanding of epileptogenesis, but also potentially illuminate new options for therapeutic developments.