Signal. I admit that the title of this blog post is somewhat misleading, but please bear with me. Yes, GLP-1 receptor agonists have very little to do with epilepsy, but there is a larger story behind this. In a recent study, nearly 28,000 people taking GLP-1 receptor agonists answered a seemingly simple question: how much weight did you lose, and how bad were the side effects? This simple survey, coupled with genetic data, produced one of the cleanest pharmacogenomic signals seen in recent years. But it also emphasized that the genetics of treatment are often not the genetics of disease, and that matters far beyond obesity and weight loss. Here is why this should make us rethink pharmacogenomics in epilepsy.
Tag Archives: SCN8A
STRIPE – When RNA Speaks Louder Than DNA
RNA. More than a decade ago, I remember reading an article arguing that we actually live in an RNA world. At the time, this felt a bit academic and not really relevant. Genetics was about sequencing and interpreting DNA. However, over the last few years, our ability to think in terms of RNA transcripts rather than DNA sequence has become increasingly relevant. When I teach trainees, I sometimes tell them: we do not care about genes. And then I pause, usually long enough to make people uncomfortable. Then I correct myself: we care about transcripts. In a recent publication, we assessed how a novel targeted long-read RNA sequencing approach can help with rare disease diagnosis. Here is what we found.
Ten Years of Accumulation: Snow-Day Thoughts Between Jonas and Fern
Decade. Over the past week, winter storm Fern has blanketed large parts of the United States with several feet of snow, leading to a virtual standstill in many regions. When I looked back, I realized that the last major snowstorm that paralyzed public life was a decade ago, a storm called Jonas. Snowed in exactly ten years ago, I reflected on the state of epilepsy genetics. Let’s see what has changed in the field since Jonas in 2016.
This was epilepsy genetics in 2021 – five things to remember
Looking back. Admittedly, I have not written an end-of-the-year review for a quite some time. However, there were a few notable moments in epilepsy genetics in 2021 that I think were worth remembering. The second year of the COVID-19 pandemic started out as a year of recovery and readjustment, only to run into unanticipated supply chain issues and novel COVID variants hanging over our transition into 2022. The scientific community was affected by these developments in different ways that made progress of science somewhat unpredictable and uneven. 2021 was the year when the phrase “unprecedented times” became stale and overused. Here are five things to remember from 2021, which will be remembered as part of a transitional phase in epilepsy genetics. Continue reading
What’s new with SCN8A – a 2016 update
An unexpected twist in the SCN8A story. SCN8A mutations were first implicated in epilepsy in 2012, when a de novo missense variant was identified in a patient with early infantile epileptic encephalopathy (EIEE) via genome sequencing. Since then, a number of patients with de novo heterozygous SCN8A variants and epilepsy have been reported, firmly establishing the role of SCN8A in EIEE, and we have learned a lot about the associated phenotype, mutation spectrum and disease mechanism within the last four years. Recently, a heterozygous familial SCN8A missense variant was identified in several families with a significantly milder epilepsy phenotype than reported in previous patients. Read further to learn more about the expanded SCN8A-associated epilepsy phenotype. Continue reading
SCN8A – this is what you need to know in 2015
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.
Publications of the week: GRIN2A, SCN8A, and DEPDC5
Issue 10/2015. This week’s publications of the week are about known epilepsy genes that have been around for a while. There are, however, some interesting updates about these genes that are worthwhile discussing. Follow me on a discussion about recent studies on GRIN2A, SCN8A, and DEPDC5. 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
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