Tilak R. ShresthaKoirala, Sunita2026-04-282026-04-282016https://hdl.handle.net/20.500.14540/26515Epilepsy is a group of disorders followed by frequent seizures. The genetic bases of epilepsy are clear from epidemiological studies and from rare gene findings. Advances in genomic technologies have facilitated genome-wide discovery of both common and rare variants which have led to a rapid increase in our understanding of epilepsy genetics. Genetic insights into the epilepsies have come primarily from Next generation sequencing (Whole exome sequencing and Whole genome sequencing) which has emerged as a building block for the identification of disease-causing mutations. In our study whole exome sequencing has been used for the screening of mutations in patients after the validation of variants to identify novel genes. Sequencing was performed on Illumina platform. After prioritization of variants, validation of variants was done by different bioinformatics analysis tools and one putative variant was screened. The causative mutation was validated by capillary sequencing and also the carrier status among the family members was checked. We ended with the prediction of the mutation in the gene to be real with the screening of eleven variants with the prediction of gene PPP2R1A to be real in family 1, the variant c.G2833A:p.E945K present in exon 17 in family 2, MAOA leading affected males for three generations with Intellectual disability in family 3, c588A>T:p.R196S and c.587G>A:p.R196K in exon 8 with mutation in gene DLG2 in family 4,c.G953A:p.R318H with mutation in ALG13 of fifth family, p.1673T with mutation of GRIA1 in family 6, c.C1058T:p.A353V as the causing factor of mutation in DPYSL3 in family 9 and , a novel gene ATP6V1B2 in family 11 and the cause of the disorders. Most of these genes are expressed in the brain and instruct subunits of ion channels that play vital roles in stabilizing and propagating neuronal activity. Disruption of these genes in general induces neuronal hyper excitability, thus causing seizures. Epilepsy syndromes are found to be the result of severe mutations in single genes whereas more commonly epilepsy is likely to be caused by the combined effect of variants in number of genes. Key words: Epilepsy, Mutation, whole exome sequencing, novel genes, seizures.en-USMutational analysisSequence variationThesis