A female Lagotto Romagnolo.
Credit: Wikimedia
MUNICH: A gene mutation discovered in truffle dogs might help scientists to understand childhood epilepsy, say Finnish scientists.
About 1 in every 200 children develops epilepsy between the age of 2 and 10, but then the seizures suddenly stop. Scientists think that there is a genetic basis to most epilepsies that aren't associated with brain injury or trauma, but they don't have an explanation for the puzzling trend of remission.
A genetic mutation found to cause epilepsy in Lagotto Romagnolo puppies may be a new candidate gene for human benign childhood epilepsies characterised by seizure remission.
"This gene discovery is significant for both dogs and humans. Every third Lagotto Romagnolo carries the gene mutation in its genome and we have now developed a gene test to be used by breeders to eliminate the disease from the breed," said geneticist Hannes Lohi from the University of Helsinki in Finland and lead author of the paper published in PLoS Genetics.
"Furthermore, the gene has not previously been linked to human epilepsies, which makes it a new candidate gene for especially childhood epilepsies."
Pure-breeds ideal candidates
Scientists suspect there may hundreds of different genes that cause epilepsy. One way of looking for these is by studying dogs, which can also be affected by epileptic seizures.
'Pure-bred' dogs are genetically very similar, which is a great advantage for scientists looking for genes that cause disease, because the 'signal to noise' ratio in genetic comparisons between sick dogs and healthy dogs is much higher than it would be in a more genetically mixed population.
Lohi and his team studied a breed of dogs called Lagotto romagnolo - also known as truffle dogs, for their ability to sniff out the prized fungi. Some Lagotto dogs start having seizures when they are 5-9 weeks old, but the fits stop by four months, which is a similar pattern, in dog age, to human remitting epilepsies in people.
Linking directly with remission
The researchers compared the genes of 11 dogs with epilepsy and 11 healthy dogs, and found a mutation in a gene called Lgi2 in the affected dogs. By testing more dogs, they concluded that if both copies of the gene are mutated, this causes the epilepsy.
"So far we only know the genes behind about 1% of childhood epilepsy patients, and this is first gene that we can link directly to remission," said Lohi. He hopes that studying this mutation will provide new information on the neurobiology of epileptic seizures.
The Lgi2 gene encodes for a protein, LGI2, which is secreted by brain cells called neurons and helps to control synapses - chemical connections between brain cells.
"The Lgi2 mutation is exciting because almost all mutations associated with epilepsy that we know about so far are in genes coding for ion channels, not secreted proteins," said Ruth Ottman, a genetic epidemiologist at Columbia University in New York. Ottman's group previously found that a mutation a similar secreted protein, LGI1, causes epilepsy in people, although this form of epilepsy comes on mostly after the age of 10. She said these findings show that faults in different parts of the brain can lead to epilepsy.
serious inaccuracy
You say "Scientists know that most epilepsies are genetic,"
This is misleading at best and probably untrue. I work for an epilepsy organisation. Epilepsy may be caused by birth trauma, brain damage, accidents, brain tumours, damage to blood vessels in the brain or other reasons.
Some types of epilepsy may be genetic in origin, but root causes are unclear for many cases of epilepsy. There is also evidence that some people may not inherit epilepsy, but they could inherit a susceptibility to epilepsy and it would still need an environmental factor to cause epilepsy in those people.
Anyone worried should talk to their doctor or contact an epilepsy charity or NGO.
Inaccuracy addressed
Thanks for letting us know, we have contacted the author of the story and have edited that sentence to be more clear.
Becky Crew
Online Editor
inaccuracy about number of epilepsies that are genetic
Thanks to the commenter for picking this up - my apologies for this inaccurate wording. It is absolutely correct that many epilepsies have an identifiable cause, such as brain injury or trauma, as the commenter points out. But both Hannes Lohi and Ruth Ottman told me in interviews that anywhere from 40-70% of epilepsies show no clear association with injury, and scientists think that there is a genetic basis to most of these cases. I hope that helps clarify the story. Thanks for reading! Marian.