This was epilepsy genetics in 2022

Looking back. This is our final blog post for 2022 and a good opportunity to look back at what happened in the last 12 months in epilepsy genetics. In brief, it was a busy time and if I were to look back at 2022 in a few years, I would probably characterize this year as a transitional year. Antisense oligonucleotides, gene therapies, and other novel treatments are on the horizon, but the field is not quite there yet. For this blog post, I would like to put the focus on five discoveries in 2022 that did not receive as much attention on our blog as they probably should have. Continue reading

Here are the most frequently read blog posts in epilepsy genetics

2022. In December, our blog passed an important milestone – one million views. Given that Beyond the Ion Channel is a niche blog on epilepsy genetics and pediatric neurogenetics, this is a milestone that we are proud of. In the current post, we would like to examine some of the trends on what people read on our blog. Given that this resource has been around for more than a decade, the topics and genes that people searched for reflect some interesting patterns in the field that may tell us about how information on genetic epilepsy is presented online and what we need to do better. Here are top five most frequently read posts, including some topics that surprised us. 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

Revisiting the phenotypic gap – the value in absent phenotypes

Phenotypic bottleneck. This is another post in the “phenotypic atomism series,” what has become our lab’s philosophy in how we think about and work with longitudinal clinical data. However, before we introduce another dimension to the phenotypic atom, let me first revisit the idea of the “phenotypic bottleneck” – a concept that had piqued my interest three years ago and led me to join the lab. In brief, in contrast to established pipelines for large-scale analysis of sequencing data, our ability to analyze clinical data at scale remains more limited. As a result, phenotypic characterization lags behind gene discovery, even with tremendous progress in the last few years. A major challenge stems from the inherent nature of working with multi-dimensional longitudinal clinical data: it can be sparse and incomplete at times. However, how much of the unknown is truly unknown?

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AES 2022 – Soundbites from Nashville, Tennessee

Music City. This year’s Annual Meeting of the American Epilepsy Society (AES) took place in Nashville, Tennessee. With a pre-meeting in Memphis and the annual Clinical Skills Workshop as the final event of the annual meeting, our team was able to spend more than a week in the Volunteer State. Yes, there is more than enough music in Nashville and it is virtually impossible to step into a pub, restaurant, or Honky Tonk without live music. Now that my ears have recovered, here is a summary of epilepsy genetics at AES 2022. Continue reading