Hannes Lohi, Edwin J Young, Susan N Fitzmaurice, Clare Rusbridge, Elaine M Chan, Mike Vervoort, Julie Turnball, Xiao-Chu Zhao, Leonarda Ianzano, Andrew D Paterson, Nathan B Sutter, Elaine A. Ostrander, Catherine André, Diane Shelton, Cameron A. Ackerley, Stephen W. Scherer, Berge A. Minassian
Epilepsy afflicts 1% of humans and 5% of dogs. We report a canine epilepsy mutation and evidence for the existence of repeat-expansion disease outside humans. A canid-specific unstable dodecamer repeat in the Epm2b (Nhlrc1) gene recurrently expands, causing a fatal epilepsy and contributing to the high incidence of canine epilepsy. Tracing the repeat origins revealed two successive events, starting 50 million years ago, unique to canid evolution. A genetic test, presented here, will allow carrier and presymptomatic diagnosis and disease eradication. Clinicopathologic characterization establishes affected animals as a model for Lafora disease, the most severe teenage-onset human epilepsy.