2248: Identification of a Novel Juvenile Myoclonic Epilepsy Gene and Its Underlying Disease Mechanism

Grant Status: Closed

Grant Amount: $82,240
Hannes T Lohi, PhD; University of Helsinki and the Folkhälsan Institute of Genetics
May 1, 2016 - October 31, 2017

Sponsor(s): Rhodesian Ridgeback Club of the United States, St. Bernard Club of America

Breed(s): Rhodesian Ridgeback, -All Dogs
Research Program Area: Neurology, Epilepsy Initiative
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Epilepsy is the most common neurological disease in dogs and affects almost all breeds. Genetics is likely to play a major role in seizure risk, and gene discovery remains as an important goal to better understand the disease and its treatment. However, genetic breakthroughs have been rare partially due to incomplete clinical diagnostics to identify true cases and controls, or to distinguish specific syndromes for genetic analyses. We have recently utilized an advanced wireless video-EEG approach in clinical studies to identify juvenile myoclonic epilepsy (JME) in Rhodesian Ridgebacks with characteristic epilepsy phenotype, age of onset and photosensitivity. The pedigree established using the JME cases suggests a strong genetic contribution and is supported by our preliminary genetic data that proposes a novel disease locus and a deleterious mutation in a neuronal candidate gene. These promising early findings necessitate further electroclinical and genetic studies for confirmation. In this study, the investigators’ objectives are to: i) further characterize EEG, imaging and disease features of JME, ii) confirm the presence and segregation of an epilepsy gene, iii) investigate the breed-specificity, prevalence and penetrance of the mutation, iv) conclude the inheritance model, and v) define the pathogenicity of the mutation. The confirmation of the genetic defect would allow us not only to develop a genetic test for breeding purposes but also to understand how myoclonic seizures develop. This could ultimately lead to improved treatments for canine epilepsy.


James, F. M. K., Cortez, M. A., Monteith, G., Jokinen, T. S., Sanders, S., Wielaender, F., … Lohi, H. (2017). Diagnostic Utility of Wireless Video-Electroencephalography in Unsedated Dogs. Journal of Veterinary Internal Medicine, 31(5), 1469–1476. https://doi.org/10.1111/jvim.14789
Wielaender, F., James, F. M. K., Cortez, M. A., Kluger, G., Neßler, J. N., Tipold, A., … Fischer, A. (2018). Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs. Journal of Veterinary Internal Medicine, 32(1), 428–432. https://doi.org/10.1111/jvim.14892
Wielaender, Franziska, Sarviaho, R., James, F., Hytönen, M. K., Cortez, M. A., Kluger, G., … Lohi, H. (2017). Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1. Proceedings of the National Academy of Sciences, 114(10), 2669–2674. https://doi.org/10.1073/pnas.1614478114

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