Cav2.1. Among the various neurogenetic disorders that we follow in our clinic, CACNA1A-related disorders are somewhat unique. Even though these conditions have been known for several decades, our understanding has remained fragmented, and the functional effect of most missense variants is still not well understood. In a recent study, we contributed to a comprehensive functional assessment of 42 missense variants in CACNA1A, approaching the problem in a structured, top-down manner. Here are the main findings from our study.
Tag Archives: CACNA1A
Glymphatic System, Mirror Neurons, and Other Stories We Tell Ourselves
Glymphatic. I stumbled over the term glymphatic system last week and briefly had to pause. The concept is now widely used and feels intuitive, but it did not exist when I was in medical school. The term was only introduced in 2012 to describe a glia-dependent, perivascular clearance pathway in the brain. And yet, everything it refers to, including perivascular spaces, astrocyte endfeet, cerebrospinal fluid flow, interstitial clearance, was already in the textbooks. All the parts were familiar to me, but the label was new. That moment of confusion stayed with me: neuroscience moves forward not just through data, but also through names.
Different genes, convergent processes – rare disease lessons from neurogenesis
A paradox in the hippocampus. Immature dentate granule cells are often described as the “plasticity reserve” of the hippocampus. They provide a pool of neurons that integrate into existing circuits, supporting learning, memory, and repair. In neurological disease, these cells have been suggested to buffer against injury or degeneration. In a recent publication, researchers showed that the hippocampus continues to generate new neurons throughout life, but that the molecular instructions for doing so vary dramatically across species. The surprising finding is this: the processes of neurogenesis are conserved, while the genes underlying these processes are often completely different. This is an important reminder that biology often converges at the level of function, even when the building blocks are not the same.
CACNA1A-related hemiplegic migraine—the big unknown
FHM. There are few neurological phenomena that are as perplexing as CACNA1A-related hemiplegic migraines. Neither migraines, seizures, nor strokes, CACNA1A-related hemiplegic migraines are poorly characterized neurological events that often defy explanation. In a recent publication, we characterized how hemiplegic migraines in children with CACNA1A-related disorders present across time. Here is what we found.
CACNA1A: the unusual tale of two proteins encoded by a single gene
CACNA1A. CACNA1A is a large gene with a long history. Its first gene-disease association was with spinocerebellar ataxia type 6 (SCA6), an adult-onset progressive neurological disorder. Next, it was found to be associated with episodic ataxia and familial hemiplegic migraine. It took several more years before it was also found to be associated with epilepsy, developmental delay, and a more severe form of hemiplegic migraine. Here is a blog post on the range of neurological disorders associated with CACNA1A and the mechanism driving it.
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
CACNA1A, hemiplegia, and the genetic of migraine
FHM. Each time I mention CACNA1A and its association with migraine to clinicians and scientists outside the field of pediatric neurology or neurointensive care, I need to take one step back. Yes, CACNA1A is one of the monogenic causes of hemiplegic migraine, but the clinical condition that we are typically concerned with has relatively little to do with common migraines. In contrast, we are talking about a neurodevelopmental disorder often associated with developmental concerns, ataxia, epilepsy and episodes of hemiplegia that may results in brain swelling and can be life-threatening. This condition, typically referred to as familial hemiplegic migraine type 1 (FHM1), neither runs in families nor does it typically result in migraine features. The historical naming conventions complicate awareness of one of the most enigmatic events in neurology, which we refer to as hemiplegic migraine episodes for a lack of a better word. However, I wanted to approach CACNA1A from a different perspective, given the recent publication of a large migraine genetic study in Nature Genetics. Continue reading
CACNA1A – this is what you need to know in 2015
P/Q. This week’s gene of the week is an atypical epilepsy gene, which is the main reason that this post is only coming out on Friday rather than Monday. Even though I was initially highly motivated to put something together on CACNA1A, I soon discovered that this gene is overwhelming. CACNA1A is a gene for both a channelopathy and trinucleotide repeat disorder, a gene for early childhood-onset and late onset adult neurological disorders, and a gene responsible for both episodic neurological conditions and neurodegenerative diseases. I have tried to put this into a coherent format. Here is what you need to know about CACNA1A in 2015. 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
Publications of the week – GABRG2, CACNA1A, and ALG13
Issue 5/2015. Each of these three genes may ring a bell, but the context in which they were described this week is new. Here is our overview of some of the most relevant publications this week. Continue reading