STXBP1 – your questions for the Channelopathist

Controversy. Our recent post that featured our Neurology publication on STXBP1 generated much interest, discussion, and debate. In particular, we received feedback from the online STXBP1 parent community that our assessment of STXBP1 encephalopathy as a static rather than a degenerative disease may be incomplete. Let me try to reconcile the results of our study with the experiences that families have shared with us in the last two weeks, trying to understand how STXBP1 can be a disease with many faces and what the common features are. Continue reading

The two dimensions of STXBP1 – a 2016 update

Synaptic. This is STXBP1 week and things are currently happening in rapid succession. We are getting ready for the first STXBP1 Charity Ball and our publication in Neurology reviewing the phenotypic features of 147 patients recently came online. STXBP1 is one of the five most common genes for epileptic encephalopathies and related neurodevelopmental disorders. However, in contrast to SCN1A, SCN2A, CDKL5, or SCN8A, it has received relatively little attention in the past from the epilepsy community. Let’s revisit a common epilepsy gene that holds more secrets than most people would imagine. Continue reading

The novel gene dilemma

N-of-1. The use of whole exome sequencing has led to many of the recent genes discovered in the epilepsy field. However, in contrast to established genes or emerging genes that are found in several patients, there is a significant proportion of patients who carry de novo mutations in novel genes. In many cases, these novel genes look very suspicious. One aspect of a recent publication in Genetics in Medicine was to assess how these suspicious candidates convert to established genes over time. Continue reading

DNM1 encephalopathy – interneurons, endocytosis, and study group

Dynamin 1. De novo mutations in DNM1 coding for Dynamin 1 are increasingly recognized as a cause for epileptic encephalopathies. However, given the role of Dynamin 1 in endocytosis in a large number of cells, the precise mechanisms how mutations may result in seizures are poorly understood. Now two recent publications in PLOS Genetics and Neurology Genetics explore the functional effects of epilepsy-related DNM1 mutations. The publication of both manuscripts is also a timely reminder to announce our international DNM1 study group that has the aim to better understand the phenotype of this disease. Continue reading

Exomes on the go – adventures with wANNOVAR

Going cloud. This post is about my most recent discovery when I was trying to modernize some of the bioinformatics tools that I had on my laptop. My experience with variant annotation is a good example of the latest trend in bioinformatics: replacing precise, but difficult-to-use tools by web-based convenience – I didn’t need to install anything after all. This is a brief journey into the world of variant annotation, taking advantage of my new favorite tool, wANNOVAR and applying it to the Epi4K dataset. Continue reading

Launching the Epilepsy Genetics Initiative – Go EGI!

Launch. This week, the Epilepsy Genetics Initiative (EGI) was launched. EGI was founded by Citizens United for Research in Epilepsy (CURE) and represents a large database for diagnostic and research exomes that will guarantee regular re-analysis of exome data, which is particularly relevant for the large number of exomes that we think are negative. Here is a brief blog post why all exomes should eventually find their way into EGI. Continue reading

Cause or coincidence – recessive SCN1A variants in Dravet Syndrome

Recessive epilepsies. Dravet Syndrome is one of the most prominent genetic epilepsies and presents in the first year of life with prolonged fever-associated seizures. Haploinsufficiency of SCN1A, either through mutations or deletions, is the major cause of Dravet Syndrome. In a recent publication in the European Journal of Pediatric Neurology, two families with recessive Dravet Syndrome and biallelic SCN1A variants are reported. Let’s have a look at how to interpret these findings. Continue reading

Publications of the week – Dravet Syndrome, TBC1D24, and CSTB

Issue 6/2015. Publications from the most recent issue of Epilepsia are very prominent in this week’s selection of publications. We discuss the frequency of Dravet Syndrome, a novel family with a TBC1D24 mutation, and the role of Cystatin B (CSTB) in Juvenile Myoclonic Epilepsy. Continue reading