Auditory. The next gene in our weekly review is LGI1. We chose LGI1 for mainly two reasons. First, it is not a gene for epileptic encephalopathies, but for familial focal epilepsies and we are currently working up a large family with an LGI1 mutation. While the conditions of the mTOR pathways were discussed quite frequently, LGI1 was a little left behind. Secondly, there were various updates on LGI1 that didn’t really warrant a full post. Therefore, we have collected this in a summary post. Continue reading
Tag Archives: LGI1
A question of conformation – chemical correction of LGI1 dysfunction
ADTLE. Autosomal Lateral Temporal Lobe Epilepsy is a rare monogenic epilepsy that has epileptic seizures with auditory auras as the most impressive feature. This condition is caused in LGI1. In contrast to most other autosomal dominant epilepsies, LGI1 is not an ion channel, but a secreted protein that binds to synaptic cell adhesion proteins. Therefore, the function of LGI1 has always remained slightly mysterious. In a recent publication in Nature Medicine, the functional properties of two LGI1 mutations are modelled in mice. Allowing neurons to secrete altered LGI1 protein otherwise targeted for degradation helped recover some of LGI1’s function. Continue reading
Guilt by association: SCN1A in Temporal Lobe Epilepsy
GWAS. Genome-wide association studies investigate the association of common genetic variants with disease in large patient samples. While this approach has been very successful in many other diseases, the results in epilepsy research have been less convincing. Given the complexity of epilepsy phenotypes, selection of the right epilepsy phenotype has been an ongoing debate. Now, a recent study in Brain finds an intronic variant of the SCN1A gene that is associated with Temporal Lobe Epilepsy (TLE), the most common epilepsy in man. Interestingly, the association with SCN1A seems to be specific for only a particular subtype of focal epilepsies. Continue reading
Familial Partial Epilepsy with Variable Foci and mutations in DEPDC5
A long story, a complicated phenotype. Massive parallel sequencing technologies were an innovation in neurogenetics and made the discovery of many genes underlying familial epilepsies possible. However, some epilepsy syndromes turned out to be more “stubborn” than others. Now, in a back-to-back submission in Nature Genetics, two groups report on the gene underlying Familial Partial Epilepsy with Variable Foci (FPEVF). And no, it’s not an ion channel this time. Continue reading
What’s the Frequency, Kenneth? The story of LGI1
Can’t you hear the radio? “S.W. was spending an afternoon at this girlfriend’s house when he suddenly heard a radio sound in his right ear. He asked his girlfriend whether she was aware of this sound as well, but he could not understand her answer. S.W. then lost consciousness and convulsed. He presented with a second seizure several months later. S.W. was started on carbamazepine and remained seizure-free. Interestingly, his mother had seizures starting at the same age. Furthermore, his sister had her first seizure at the age of 8 years and frequently reported auras where she would see colourful pictures and hear noises like a familiar song. These episodes sometimes occurred seconds before she had a generalised tonic-clonic seizure.”
LG-what? This impressive case report taken from Steven Waxman’s Molecular Neurology illustrates a family with lateral temporal lobe epilepsy (LTLE), a rare form of seizure disorder in which auditory features often precede a generalized tonic-clonic seizure. Auditory or acoustic features including radio sounds, machine noises or more complex acoustic phenomena arise from the lateral temporal lobe, a part of the brain important for auditory processing. During a discussion with one of our students last week, I realised that even though we frequently write about microdeletions and novel gene findings on the EuroEPINOMICS blog, some of the classics of epilepsy genetics may sometimes be revisited as well. LTLE is the premier example that genetic epilepsies are not neccesarily due to ion channels. Continue reading
