The Role of Whole Exome Sequencing in the Diagnosis of Epileptic Encephalopathies

Objective: Epileptic encephalopathies are a devastating group of electroclinical syndromes with early onset of drugâ?resistant seizures in which the epileptiform abnormalities may contribute to progressive dysfunction or developmental stagnation and consequent cognitive and behavioral impairments. 

A genetic etiology can be identified in a considerable proportion of patients with epileptic encephalopathy. Most have de-novo dominant mutations, but a growing proportion of patients has a polygenic inheritance in which the interaction of several genetic variants is responsible for the phenotype.

The increased efficiency and the reduced cost of next-generation sequencing tests promoted their implementation into the routine diagnostic process.  Whole-exome sequencing (WES) is a technique for comprehensively sequencing all the protein-coding regions of the genome (~20,000 genes). It has proven successful in identifying undiagnosed genetic disorders in many patients with a broad phenotypic spectrum.

Methods: We report our experience in the use of WES as a first-tier molecular test in 40 patients with undiagnosed epileptic encephalopathies at Oasi Research Institute-IRCCS, Troina, Italy. The test was performed on probands and their unaffected parents (trio analysis). Each genetic variant found has been compared to known variables in main polymorphism and mutation databases and a deeply in silico analysis for predicting pathogenicity was performed. All variants found were confirmed by sanger sequencing.


Results: About a third of patients received a genetic diagnosis. And WES proved to have a good cost-effectiveness ratio. Our data highlight the clinical utility and feasibility of WES in individuals with undiagnosed forms of epileptic encephalopathies.


Luigi Vetri

Abstract | PDF

Share this  Facebook  Twitter  LinkedIn  Google+
Recommended Conferences
Google scholar citation report
Citations : 9

Insights in Neurosurgery received 9 citations as per google scholar report

Abstracted/Indexed in
  • Google Scholar
  • Directory of Research Journal Indexing (DRJI)
  • WorldCat
  • Secret Search Engine Labs

View More »

Flyer image