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.
Tag Archives: SCN1A
This is what you should know about KCNT1 – a 2015 update
Dual phenotypes. When KCNT1 was first described as a gene for Migrating Partial Seizures of Infancy in 2012, it wasn’t just a novel gene for epileptic encephalopathies. In parallel, the same gene was found to underlie a novel subtype of autosomal dominant nocturnal frontal lobe epilepsies (ADNFLE). At the time, this left us scratching our heads how a gene could cause such distinct, but entirely separate phenotypes. In a recent publication in Epilepsia, Møller and collaborators revisit the phenotypic spectrum of KCNT1. They find that both phenotypes can occur within a single family and that KCNT1 mutations can result in other phenotypes, adding to the mystery of KCNT1. Continue reading
GABRB3, 15q dups, and CNVs from exomes
GABAergic. Let’s start out with a provocative statement. There is a single gene that may explain more cases of Lennox-Gastaut Syndrome (LGS) and Infantile Spasms (IS) than you would expect, rivalling SCN1A for the most common gene found in this group of patients. It’s a gene that you are probably aware of but that you may think to be a very rare finding. In a recent publication in Annals of Neurology, the Epi4K consortium published their recent analysis of copy number variations that were derived from exome data. Combining de novo mutations and copy number variations points to GABRB3 as a major player in LGS and IS, explaining probably more than 2% of patients. Let’s find out about the twilight zone, strategies to obtain structural variants from exomes, and the re-emergence of the 15q duplication syndrome. Continue reading
Publications of the week: SCN8A, SYN1, ZDHHC9, and SCNM1
Power outage. This week’s publications of the week were conceptualized in complete darkness. A thunderstorm had hit the Philadelphia area on Tuesday, leading to widespread power outages in the region. I found myself in the strange position of being without power for a night, but with full strength cell phone reception and a completely charged laptop battery. Here is our post on the most relevant publications of the last few weeks, written in the calm of a dark night where the only sound around was the howling of our neighbor’s backup generator. 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
SCN1A and Dravet Syndrome – your questions for the Channelopathist
Comments. After posting our 2015 update on what you should know about SCN1A, we received a number of comments on our blog and by email. We usually have the policy to respond to every comment individually. However, after we had realized that we had fallen behind with a few replies for several weeks, we felt that it might be worthwhile rephrasing some of the questions as general topics to write about, especially since many of your questions raised interesting points. Here are the questions that you asked regarding SCN1A and Dravet Syndrome. Continue reading
SCN1A – this is what you should know in 2015
2015 update. Our updates on SCN1A mutations and Dravet Syndrome are amongst our most frequently read posts. Therefore, following the tradition of annual reviews that we started last year, we thought that a quick update on SCN1A would be timely again, building on our previous 2014 update. These are the five things about SCN1A that you should know in 2015. Continue reading
Discrepancies in interpretation – when can exomes speak from themselves?
Interpretation. There is huge promise in discovering the genetic basis of neurodevelopmental disorders using exome sequencing, but it is often not clear how ambiguous results are communicated to families. In a recent publication in Clinical Genetics, the authors try to understand what happens to exome results as they land on the clinician’s desk – and leave us with the conclusion that diagnostic exome sequencing when reviewed in a clinical setting may have a false positive rate of up to 20% with 5% of false negatives. 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
How to get started in epilepsy genetics – The Channelopathist’s third birthday
Happy birthday. The Channelopathist turned three last week, i.e. exactly three years ago we started writing regular blog posts on epilepsy and genes, starting with a post on how SCN2A was rediscovered in neurodevelopmental disorders. Since we had many new subscribers last year, I thought that I could use this opportunity to write a brief post on how you can get started on Beyond The Ion Channel and how you can navigate our blog. Continue reading
