Canine epilepsy gene identified

A study led by LUPA Finnish scientist Hannes Lohi (inset), in collaboration with research groups from Sweden and Switzerland, has identified a mutation in a novel gene as the cause of a genetic-idiopathic epilepsy syndrome in the Lagotto Romagnolo dog breed. In a recent publication in PLoS Genetics, an epilepsy-associated mutation in LGI2 was shown to prevent the protein’s secretion which can result in a destabilized neural network that is prone to seizures. LGI2, like its homolog the human epilepsy gene LGI1, was demonstrated to encode a secreted protein that interacts with known neurological receptors. However, unlike LGI1, LGI2 is predominantly expressed during the immediate post natal period implying that its function may be more important during the neural network construction phase.
Epileptic seizures constitute one of the most common neurological disorders in both dogs and children. Given its various complex pathologies, it has been difficult to elucidate the genetic and molecular basis of the disease. As the disorder is enriched in several isolated canine breeds, the dog with its more homogenous genetic architecture presents as a good model to study and understand familial epilepsies.In the Lagotto breed, a curly-haired dog initially selected for game water retrieval and truffle hunting traits, the epileptic disorder investigated is characterized by an onset at seven weeks and a highly predictable remission at four months. The LGI2 gene represents the first identified gene for focal epilepsy and a DNA test for the Lagotto breed is now commercially available through Genoscoper Oy (Ltd).

Two of the most common forms¬† of children’s epilepsy, Rolandic Epilepsy and Panayiotopoulous Syndrome, are known to occur during the 2-10 year age period which is the equivalent age range of the Lagotto epilepsy manifestation. Both canine and human disorders present similar pathologies. Thus, LGI2 may likewise be considered as a candidate gene for some forms of human juvenile epilepsy.

Complete details of this study are available from the open access journal PLoS Genetics. This work is highlighted on Cordis News (press released prepared by the European Commission) and in the open journal Disease Models and Mechanisms.