A TARGETED ANALYSIS APPROACH TO WHOLE EXOME SEQUENCING FOR EPILEPSY DIAGNOSIS

Background:
Epilepsy classifies a number of seizure disorders caused by excessive and abnormal brain cell activity. A total of 70–80% of all epileptic cases are thought to be caused by one or more genetic mutations, catering to a highly variable phenotypic expression. Recent advancements in next generation sequencing (NGS) have contributed to an increased understanding of the genetic contribution to epilepsy disorders. Despite this, as yet, no accurate and cost-effective diagnostic test exists. The development of such a test would have significant prognostic implications for patients and their families. Aim: This study aims to apply a whole exome sequencing (WES) approach to epilepsy diagnosis using targeted analysis of ∼395 genes identified to be associated with epilepsy.

Methods:
WES was completed on 20 samples using the Ion AmpliSeqTM Exome RDY Kit. All data were analyzed using an in-house bioinformatic pipeline, analyzed following filtering and prioritization of variants based on gene ontology, associated pathways, minor allele frequencies, and a number of in silico predictive functional scores. Initial work focused on four samples with a known SCN1A gene mutation previously identified using our NGS diagnostic neurogenetic panel. An additional 16 samples with no mutation in the SCN1A gene were then examined by WES and targeted analysis in an effort to identify mutations in other potential genes contributing to their epilepsy phenotype.

Conclusions:
It is hoped that this research will develop an improved diagnostic test for epilepsy patients and provide more refined treatment options.