SCN8A. In 2015, SCN8A has emerged as an important gene in epileptic encephalopathy. SCN8A encodes the voltage-gated sodium channel alpha subunit Nav1.6, and was first implicated in epileptic encephalopathy in 2012. Since then, approximately 100 cases of early-infantile epileptic encephalopathy caused by mutations of SCN8A have been identified, and the disorder has been designated EIEE13. Here is what you need to know about SCN8A in 2015.
Issue 13/2015. Our pick for the publications of the week includes a recent publication on the felt stigma of epilepsy and genetic attribution. We also review a major publication on the broadening spectrum of SCN2A related epilepsies and one of the first reports of WDR45 mutations in male patients with epileptic encephalopathy.
GABA/glutamate. Even though large-scale Copy Number Variation (CNV) studies in schizophrenia, autism, and intellectual disability were en vogue only a few years ago, it became quiet around these type of studies more recently. Now, a recent study in Neuron revisits CNV analysis in schizophrenia with the largest sample size to date, cancelling out much of the noise that smaller studies had to fight with. Find out how the authors managed to demonstrate a contribution of the GABAergic and glutamatergic system to schizophrenia by sheer numbers. Continue reading
GLUT1DS. The next gene in our list of Epilepsiome genes is SLC2A1, coding for the major glucose transporter in brain and erythrocytes. Initially thought to be exclusively associated with a very rare and severe epileptic encephalopathy, recent studies have suggested that SLC2A1 mutations can also be identified in patients with early-onset generalized epilepsies and familial epilepsies. Continue reading
Issue 12/2015. This issue of our publications of the week is about two new candidates for familial epilepsies and a study about the phenotypic range of one of our novel epilepsy genes. Also, I wanted to add a brief update on the progress of our Epilepsiome project.
Family studies. In July 2015, we launched a German-Israeli-Palestinian collaborative project on familial epilepsy in Israel and Palestine. This project is supported by a specific funding mechanism by the German Research Foundation (DFG) called the Trilateral Grant. I thought that I would introduce the project to you, and let you know how we are planning to overcome our current crisis in family studies. Also, find out why I initially planned to write about Beethoven. Continue reading
KCNQ2. The next ion channel gene to be reviewed in the Epilepsiome blog posts is KCNQ2, encoding a subunit of a voltage-gated potassium channel. Known for years as a gene for a familial and self-limiting neonatal epilepsy syndrome, mutations are now also shown to be a frequent cause of neonatal epileptic encephalopathy. Here is what you need to know about KCNQ2 in 2015. Continue reading
SCN2A. The next gene on our list of epilepsy genes to review is SCN2A. Within less than three years, SCN2A has risen from a gene for a very rare benign familial epilepsy syndrome to one of the most prominent genes associated with neurodevelopmental disorders to date. Epilepsies due to SCN2A mutations can have a broad range of phenotypes that are still not fully understood. Here is our 2015 post on the gene that we refer to as the genetic shapeshifter. Continue reading
Issue 11/2015. This issue of our publications of the week is about three novel genes that were published recently, including a relatively frequent cause of intellectual disability in females, a gene for spinocerebellar ataxia, and a mutation in a novel SNARE-complex associated protein. Continue reading
Epilepsiome. Two weeks ago, we had a few teleconferences about what the purpose of our gene curation and gene review efforts should be. Should we be a blog, should we be OMIM, or should we be a new neuromuscular homepage? None of these resources feel quite right for the questions that we have in epilepsy genetics. While thinking about this question, it became clear to me that we need to address five different aspects of each epilepsy gene, a framework that I’ll refer to as the 5-P concept. What is this concept about? Follow me onto a journey into the essential dimensions of interpreting the relevance of a variant in a clinical context. Continue reading