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Advancing the phenome alongside the genome in epilepsy studies

The development of high-throughput sequencing technologies has led to remarkable progress in understanding the genetic basis of human epilepsies. Over the last 5 years, more than 20 genes have been identified through genome-first approaches, identifying novel genes first and then working backwards to understand the associated phenotypes. This approach has been useful in epileptic encephalopathies, where family-based exome studies have identified a growing list of genes with causative de novo mutations.1