GAT1. The SLC6A1 gene remains one of the most common genetic etiologies to be associated with genetic generalized epilepsy and myoclonic atonic epilepsy. SLC6A1 has not received an update on our blog in a while, perhaps because unlike many other genes we see, this one has remained with a somewhat consistent clinical picture, albeit with much more detail and confidence than available back when the first papers were published in 2015-2018. Here are the five things to know about SLC6A1 in 2023.
Category Archives: Updates
SCN2A – here is what you need to know in 2023
NaV1.2 Today is International SCN2A Day, 2/24/2023. SCN2A is on the long arm (q arm) of chromosome 2 at position 24.3, hence 2/24. In honor of this day, we wanted to refresh the SCN2A gene page, which was long overdue. Much has been learned since our initial post in 2015, so in addition to the gene page, here are three things to know about SCN2A in 2023.
CHD2 – here is what you need to know in 2023
Chromodomain. Today is International CHD2 Awareness Day and we are publishing this blog post in time for our CHD2 webinar where we present the result of a four-week sprint to analyze harmonized clinical data. We also updated our gene page on CHD2, which was long overdue. In addition to becoming a more well-known gene, here are three things to know about CHD2 in 2023. Continue reading
SYNGAP1 – three things to know in 2023
Postsynaptic. SYNGAP1-related disorders are among the most common genetic developmental and epileptic encephalopathies with a unique clinical presentation. However, since the initial gene discovery in 2009, the clinical spectrum has expanded significantly to include a wider range of epilepsies and seizure types. Additionally, the SYNGAP1 community has grown to encompass hundreds of individuals reported in the literature or organized in advocacy organizations. Accordingly, we wanted to use the opportunity to update our SYNGAP1 page. Here are three things to know about SYNGAP1 in 2023.
The Great De-Siloing
Data sharing. Over time, genomic scientists have learned how to share. Large international cohorts and efforts of data deposition have led to large databases that can be used to answer big questions. However, silos of genomic data, such as massive sequencing studies performed on specialized cohorts, lay unconnected across research groups, academic institutions, and collaborators. Recently, we have been involved in several projects to de-silo rather than simply share genomic data, and we realized that there may be some aspects that apply to the genomics worlds more broadly. For example, what makes de-siloing different from data sharing? The goal of this post is to redefine these concepts and explain why we should be less concerned about data sharing and more concerned about data integration. Continue reading
DNM1 and when transcripts matter more than genes
What comes next. Earlier this month, Ingo made a bit of a splash at the American Epilepsy Society Annual Course, with his surprising comment that, in some contexts, “genes don’t matter.” This was in reference to transcripts and gene expression, which ultimately determine if and how variants can cause disease. In this post, I wanted to explore this idea, diving into the world of transcripts and their increasing relevance in approaching diagnosis and treatment of genetic epilepsies and neurodevelopmental disorders. And I wanted to share one of the most surprising findings in epilepsy genetics in 2022, namely, how examining transcripts rather than genes helped us understand how an intronic variant can be dominant-negative. Continue reading
Five things to know about PURA
PURA. The title of this blog, Beyond the Ion Channel, is intended to reflect the wide variety of genes that can cause epilepsy and related neurodevelopmental conditions. Our last post on CACNA1A brought us back to channelopathies, so this blog post will again shift our focus. This post will introduce the new gene page for PURA, a gene that we did not feature as prominently as we should have. Here are five things to know about PURA, which is relatively recent to be described as a condition, and is likely more common than originally thought.
Unlocking STXBP1 through Electronic Medical Records
Understanding the EMR. Several weeks ago, I gave a presentation at the STXBP1 Summit conference, the third annual meeting since the first in 2019 – a time when I had just entered the field of neurogenetics. It has been fascinating to follow one of the neurodevelopmental genes with the “fastest growing knowledge,” with the expanded scope of clinical studies and emergence of novel avenues for targeted gene therapies on the horizon. However, one of the many projects our STXBP1 team is currently working on takes a somewhat atypical approach – we aimed to map the natural disease history of STXBP1-related disorders based entirely on reconstructed Electronic Medical Records (EMR). Here are some of the challenges we have had to confront and what we learned searching for meaning in the depth of the EMR. Continue reading
CACNA1A – five things to know in 2022
Epilepsy genes. It has admittedly been quiet around the gene pages on our blog and many pages require an update. When we initially launched the Epilepsiome pages, we wanted to create a small resource for gene-based information according to the “what you need to know” principle, a condensed digest regarding epilepsy genes written by clinicians and researchers with deep expertise in the field. We chose CACNA1A as the first gene to get an update. The reason for this is the following: Laina has taken on the role of modernizing this blog and CACNA1A is the main condition that she is working on. Here are five things to know in 2022 about CACNA1A. Continue reading
Epilepsy genetics meets epilepsy surgery – an unexpected link
Presurgical work-up. In 2012, I gave a presentation entitled “Epilepsy genetics for epilepsy surgeons” to a group of epileptologists who mainly work in a presurgical setting. Back then, I was not sure whether anybody in the audience took anything away from this presentation. Traditionally, the thinking surrounding intractable epilepsies is divided, and epilepsies are often considered either genetic or surgical as if both categories were mutually exclusive. In fact, there are many overlaps. A recent review highlights the links between epilepsy surgery and epilepsy genetics. Continue reading