When Monogenic Isn’t Monogenic—Unravelling the Oligogenic Architecture of the Developmental and Epileptic Encephalopathies

Abstract

Comprehensive Analysis of Coding Variants Highlights Genetic Complexity in Developmental and Epileptic Encephalopathy Takata A, Nakashima M, Saitsu H, et al. Nat Commun. 2019;10(1):2506. doi:10.1038/s41467-019-10482-9. www.nature.com/naturecommunications. Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE gen..