2015 in review. This year has been a very busy year on Beyond the Ion Channel and this is my time to thank our contributors and readers. This blog and the Epilepsiome project have become an essential part of what I am doing. I am very thankful for all the feedback and advice that I have received this year. We have also finally launched the Epilepsiome project this year, the gene curation project of our epilepsy genetics community. As a summary of 2015, we have put together a summary of the most popular posts of 2015. Continue reading
The holiday season. On Dec 25th, I was forced to disable the long-range communication device of the Stellosphere – and all I had was a simple screwdriver. It was a tough choice, but when you’re out there by yourself, you have to make bold choices. If you now believe that I have a MacGyver-like engineer skillset, I hate to disappoint you. All I did was take out the batteries of one of the toys that our kids got for Christmas so it would stop making noise every time you touch it. Here are the three books that I am trying to read over the holiday season. I probably won’t get through them completely as I want to spend as much time with my family as possible, but here is what they have told me about epilepsy genetics so far. Continue reading
Completing the SCN8A spectrum. SCN1A was initially discovered in GEFS+, an autosomal dominant familial epilepsy syndrome. SCN2A was first identified in Benign Familial Neonatal-Infantile Seizures (BFNIS), also representing an autosomal dominant familial epilepsy syndrome. SCN8A, the third epilepsy-related sodium channel gene, has only been associated with severe, sporadic cases so far, not with more benign familial epilepsies. In a recent publication in Annals of Neurology, a novel recurrent mutation in SCN8A is identified, which causes benign infantile seizures and paroxysmal dyskinesia. While this finding adds the missing familial epilepsy syndrome to SCN8A, it also provides an intriguing link to the phenotypes caused by PRRT2. Continue reading
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
N=1. Even though many recessive disorders have been identified through next-generation sequencing, there is a major conceptual problem when it comes to interpreting the results of these studies. Recessive disorders are very rare and it is sometimes difficult to assess whether a given variant is truly disease-causing or simply an innocent bystander. A recent study in Nature Genetics has developed a novel concept to identify recessive disorders that rise above the overall genomic noise, finding four novel recessive disorders. In addition, the authors have enhanced their analysis by a statistical analysis of disease phenotypes.