Epilepsy Genetics Initiative

The Epilepsy Genetics Initiative (EGI) was created in 2014 with the goal of amassing a database of clinically-generated exome sequence data for patients with epilepsy who have had diagnostic whole exome sequencing. Most of the subjects enrolled in the study did not receive a secure genetic diagnosis from their initial sequencing. Following participant/family consent, EGI transfers raw data from the respective clinical lab to the Institute for Genomic Medicine at Columbia University Medical Center. The strategy of the initiative has been to carry out systematic reanalysis of data to identify new diagnoses that were not possible or missed at the time of initial sequencing and to aid in novel gene discovery in epilepsy.]]> The inclusion criteria for our study are individuals with epilepsy and their family members who have previously had diagnostic whole exome or genome sequencing. Having a genetic diagnosis at the time of enrollment is not an exclusion criterion as it is possible to receive a genetic diagnosis that is incorrect, and this cohort may be used to evaluate for genetic modifiers in the future. However, most of our participants have not received a secure genetic diagnosis following their initial sequencing.]]> The study has been ongoing since 2014. Since the study's inception, we have made eight new diagnoses for a diagnosis rate upon reanalysis of 5.8%. We have also provided new evidence for several previously reported findings to either support or contradict the evidence of a variant's pathogenicity, and we have highlighted new gene-disease associations for several participants. EGI has also published a paper implicating variants in the alternative exon 5A in the SCN8A as associated with epileptic encephalopathy (PMID 29121005). The initiative also contributed a case to facilitate the implication of the PPP3CA gene with disease (PMID 28942967).]]>