Three things I learned about focal epilepsies on the Faroe Islands

Focal to genetic. While there was little interest in the genetics of focal epilepsies only five years ago, the field has gained significant momentum since the discovery of DEPDC5 and the subsequent new appreciation of the mTOR pathway. This finding resulted in several gene discoveries and linked traditional genetic epilepsies with the emerging field of somatic mutations. In May 2017, the European epilepsy genetics community met on the Faroe Islands for the international conference on focal epilepsy. Here are the three things that I learned about focal epilepsies on the Faroe Islands. Continue reading

DEPDC5 – this is what you need to know in 2015

DEPDC5. We have selected DEPDC5 to be our gene of the week. DEPDC5 is currently the most common known gene for focal epilepsies. DEPDC5 mutations cause familial focal epilepsy with variable foci, an epilepsy syndrome with autosomal dominant inheritance where the affected family members can have different types of focal epilepsies, most frequently frontal lobe epilepsy. Despite seizure semiology that varies among family members, it is constant for each individual. Continue reading

Publications of the week – CNTNAP2, DEPDC5, and autism whole-genome sequencing

Issue 4/2015. Trying to keep up with the publications of the week in the field, we have selected three manuscripts this week, which challenge some of our well-established beliefs. It’s about an autism gene losing its statistical support, a familial epilepsy gene rediscovered in focal cortical dysplasia, and the surprises of whole-genome sequencing in familial autism. Continue reading

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

2013 in review: top three lists and the gene finding of the year

Gene of the year. Let’s take a minute to look back at the very busy year of 2013. There were major advances in many areas of epilepsy genetics. First and foremost, massive (and I mean massive) progress has been made in the genetics of the epileptic encephalopathies, where de novo mutations have been identified as a major source of genetic morbidity. Secondly, the new technologies have made it possible to identify several novel genes for various epilepsy types. Out of these genes, we have again selected the most important finding in 2013. And the gene finding of the year is… 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