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
Tag Archives: STXBP1
This was AES 2021 – five takeaways from Chicago
Pandemic. This year’s Annual Meeting of the American Epilepsy Society (AES) was the 75th meeting, but it was a meeting like no other. #AES2021 was the first in-person meeting for the international epilepsy community with many international participants unable to join due to local restrictions and the US-based audience split between participating in-person and joining remotely. However, despite the unusual format, this year’s meeting was bustling and full of excellent science. Here are my five takeaways from AES 2021. Continue reading
STXBP1-related disorders: deciphering the phenotypic code
STX. Neurodevelopmental disorders due to disease-causing variants in STXBP1 are amongst the most common genetic epilepsies with an estimated incidence of 1:30,000. However, despite representing a well-known cause of developmental and epileptic encephalopathies in the first year of life, relatively little has been known about the overall genetic landscape and no genotype-phenotype correlations have been established. In our recent publication including almost 20,000 phenotypic annotations in 534 individuals with STXBP1-related disorders, we dive deep into the clinical spectrum, examine longitudinal phenotypes, and make first attempts at assessing medication efficacy based on objective information deposited in the Electronic Medical Records (EMR), including information from the almost 100 “STXers” seen at our center in the last four years. Continue reading
Entering the phenotype era – HPO-based similarity, big data, and the genetic epilepsies
Semantic similarity. The phenotype era in the epilepsies has now officially started. While it is possible for us to generate and analyze genetic data in the epilepsies at scale, phenotyping typically remains a manual, non-scalable task. This contrast has resulted in a significant imbalance where it is often easier to obtain genomic data than clinical data. However, it is often not the lack of clinical data that causes this problem, but our ability to handle it. Clinical data is often unstructured, incomplete and multi-dimensional, resulting in difficulties when trying to meaningfully analyze this information. Today, our publication on analyzing more than 31,000 phenotypic terms in 846 patient-parent trios with developmental and epileptic encephalopathies (DEE) appeared online. We developed a range of new concepts and techniques to analyze phenotypic information at scale, identified previously unknown patterns, and were bold enough to challenge the prevailing paradigms on how statistical evidence for disease causation is generated. Continue reading
GNAO1 and 13K genomes – rare disease sequencing on a national level
WGS. Whole-genome sequencing is increasingly used to understand the cause of rare diseases in a research and diagnostic context. However, while the usefulness of this technology has been shown in smaller studies, it remains unclear whether strategies to understand the cause of rare disorders through whole genome sequencing can be performed on a national level. A recent study in Nature reported the first results from a national sequencing campaign for rare disorders in the UK, including the analysis of more than 13,000 genomes. In this blog post, I would like to focus on the neurogenetics component of this enormous study, which identified disease-causing variants in GNAO1 as the most common cause within the study’s subgroup of neurological and developmental disorders. Continue reading
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
STXBP1 – this is what you need to know in 2015
STXBP1. The next candidate in our weekly review of epilepsy genes is STXBP1. This gene was initially discovered in 2008 as cause for Ohtahara Syndrome. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far. Here is what you need to know about STXBP1 in 2015. Continue reading
Publications of the week: RBFOX1, THOC2, and exome sequencing in Infantile Spasms
Issue 8/2015. This week’s review of the relevant publications in the field is about a novel risk factor for focal epilepsies, a gene involved in mRNA transport from the cell nucleus, and a small, confirmatory study on exome sequencing in Infantile Spasms.
