Grant: Institute of Genetics Clinical Investigatorship Award

Advances in genetic sequencing have taken a tremendous leap forward with the advent of next generation sequencing. It is now possible to sequence an individual's entire coding sequence, or "exome", quickly and inexpensively. The technology has been successful in identifying disease genes in rare Mendelian traits. Idiopathic generalized epilepsy (IGE) is a complex condition with a marked familial aggregation and high concordance in identical twins. This strongly supports a genetic contribution to this common condition. A few genes have been identified in individuals with a family history of IGE. When these genes are tested in cases with no family history, there are individuals with new, or de novo, changes at the epilepsy genes. We plan to sequence the exome of children with idiopathic generalized epilepsy. We will also sequence their unaffected parents. Any changes we observe in the child with IGE but not present in the parents would qualify as an epilepsy gene candidate for a de novo mutation. We will also explore how well this new technology performs as a potential diagnostic tool for IGE. If we have a readily available, cheap and quick method of identifying epilepsy mutations, we may halt further investigations for a child and their family. The knowledge may tailor the anti-epileptic medication, provide clarity with regards to long term prognosis, and give information for genetic counseling purposes.