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
Tag Archives: RELN
Untying the Gordian knot – the return of Reelin
RELN. Amongst the various genes implicated in neurodevelopmental disorders, Reelin (RELN) has always been one of the more controversial genes. While bi-allelic variants have been implicated in lissencephaly with cerebellar hypoplasia, the role of autosomal dominant variants has been controversial and is currently considered disputed. Reelin is a relatively large gene – accordingly, missense variants are frequent. However, a recent study suggests that the picture might be more complicated and that both monoallelic and bi-allelic variant in Reelin may contribute to neurodevelopmental disorders. Here are my thoughts. Continue reading
TADA – a joint analysis of de novo and inherited risk factors in autism
Beyond de novo. One of the most robust ways to interpret exome data is the analysis of de novo mutations. However, in addition to the 1-2 de novo events that we can identify in every individual, there is a plethora of inherited variants that often look suspicious. Unfortunately, other than looking at monogenic recessive disorders, we are often incapable of understanding the importance of these inherited variants and tend to ignore them. A recent publication in Nature now overcomes this difficulty by applying a joint analysis of inherited and de novo variants in autism. Continue reading