Identification of Underlying Genetic Mutation in a Case of Familial Epilepsy

Abstract

Epilepsy is a chronic neurological condition characterised by recurrent unprovoked seizures and often associated with cognitive dysfunction. The major underlying factors include genetic factors, head trauma, infections, and brain disorders. The present case-study involves a family in which multiple members are affected in different generations suggesting a strong inherited genetic component. The proband’s electroencephelography demonstrated frequent epileptiform activity and so this study aims to identify the underlying genetic variants in case of familial epilepsy using targeted exome sequencing which consists of a gene panel covering 5649 genes including genes associated with epileptic encephalopathy genes as well. Total 27 pathogenic mutations were identified in 26 genes. Out of these 27 mutations, seven pathogenic mutations DPYD (c.85T>C), BBS2 (c.209A>G), GLI2 (c.4558G>A), CLN6 (c.214G>T), PRODH (c.1562A>G), HEXB (c.185C>T), and MAG (c.399C>G) are associated with neurological disorders as per OMIM database. Remaining mutations are reported to be associated with congenital, muscular, metabolic, immunodeficiency disorders, etc. It may suggest that the proband might develop other complications as well. The analysis of a proband with unidentified genetic anomaly provided list of sequence variants for further functional investigation to understand the complex molecular mechanism underlying this familial occurrence epilepsy.