Research locates possible genetic cause for myoclonic epilepsy

A genetic cause for myoclonic epilepsy syndrome in Rhodesian Ridgebacks could benefit both the veterinary industry and human medicine.

In a collaborative study conducted by the University of Helsinki, the Ludwig Maximilian University in Munich, and the University of Guelph, researchers studied myoclonic epilepsy syndrome in dogs and genetic analysis revealed the DIRAS1 gene as the cause. As myoclonic epilepsies are one of the most common forms of human epilepsy, the study reveals a candidate gene for the disorder in people and a model to further elucidate the role of DIRAS1. The study was published in the Feb. 2017 issue of Proceedings of the National Academy of Sciences of the United States of America.

The study specifically tested Rhodesian Ridgebacks, as “the presence of multiple affected dogs with a distinct phenotype in many litters proposed an inherited condition” and warranted a comprehensive study. It included 95 dogs with an early onset of epilepsy, starting when the dogs were an average of six months old.

The epilepsy is observed in what are described as myoclonic jerks or twitches, which mainly occurred when the dogs were lying down, relaxed, drowsy, or in the first stages of sleep. Researchers used a video-EEG system to observe the dogs for periods of time greater than an hour. Myoclonic twitches occurred during observation in all but two recordings.

Light sensitivity could also play a role, as visually induced seizures were reported in 8 of 23 observed dogs. In these instances, visual stimuli, such as light flashes and light coming in through opened shutters in the morning, triggered myoclonic seizures.

To identify the genetic cause, researchers combined a genome wide association study (GWAS) and next-generation sequencing analyses using whole-exome (WES) and whole-genome (WGS) resequencing. According to the study, “Only one nonsynonymous variant was found, a 4-bp deletion in the exon 2 of the DIRAS1 gene.” Researchers then genotyped an additional 498 Rhodesian Ridgebacks from 13 countries and found that 15% carried DIRAS1 mutation. To determine breed specificity, they tested an additional 965 epileptic dogs from 12 breeds and found no carriers. This indicated the mutation is specific to Rhodesian Ridgebacks.

Researchers concluded the clinical and genetic studies conducted identify a candidate gene for generalized myoclonic epilepsies and can give insights into the disease etiology. This will allow for future studies into DIRAS1 in humans, and the researchers advise further studies should identify DIRAS1-mediate mechanisms in neurotransmission and provide drug targets to treat common epilepsies.

Photo credit: © iStock/olgagorovenko

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