Mutation Identification for Epilepsy in the US Hispanic Population Using Whole-Exome-Sequencing

Purpose: Epilepsy, characterized by recurrent unprovoked seizures, is a common neurological disorder related to a wide variety of genetic, developmental and acquired brain conditions.Genetically determined epilepsies are associated with a multiplicity of potential genetic variants identified in predominately Caucasian populations.There has been limited research in the US Hispanics/Latino populations.Whole Exome Sequencing (WES), as a rapid and reliable means, has identified causative mutations for a number of diseases.Therefore, we applied WES to identify pathogenic mutations for epilepsy in the Latino population.Methods: Among 14 symptomatic subjects recruited from the Departments of Psychiatry and Neurology at the Texas Tech University Health Sciences Center in El Paso, Texas, 11 met the diagnosis criteria for epilepsy.WES was performed by the Illumina Nextera Rapid Capture Exome Enrichment kits, then bioinformatics predictions were conducted using the SVS program by accessing data from dbNSFP, which provides scores from multiple functional prediction programs and two conservation scores.Results: A total of 47,392 variants in exons or at splice-site boundaries were identified.After filtering, 18 non-synonymous rare variants were identified in 8 out of 11 patients.To identify high impact genes and biological pathways, further bioinformatics analysis, "hotspot" analysis and literature-based searches were conducted.The CREBBP gene and pathways, such as "cell cycle" and "Notch signaling" were suggested to be important in the pathophysiology of epilepsy.Conclusion: This WES led to the discovery of additional epilepsy genes in the US Latino population; however, future validation and segregation analysis using a family design are needed to confirm the current findings.