TBC1D24. Yes, our last blog post regarding TBC1D24 was published in 2015, but that doesn’t mean we aren’t still thinking about this elusive gene and its wide phenotypic spectrum. Today we provide an update from Joeylynn – a new research coordinator in the Helbig lab, a health care provider, co-creator of the TBC1D24 Family Foundation, and most importantly, the mother of a child with TBC1D24
Category Archives: Updates
SNAREopathies in epilepsies and neurodevelopmental disorders
SNARE complex. This is the first post in our series on SNAREopathies – an umbrella term for diseases caused by variants in the soluble NSF attachment protein receptor (SNARE) complex, that is essential for neuronal synaptic vesicle exocytosis in the presynapse. The core SNARE complex comprises a four-helix bundle consisting of two SNAP25 helices, which is encoded by SNAP25, the syntaxin 1 helix encoded by STX1A/STX1B, and the synaptobrevin 2 helix encoded by VAMP2. The complex is regulated by different proteins including MUNC18 encoded by STXBP1, MUNC13 encoded by UNC13A, and synaptotagmin encoded by SYT1 and complexins. Here is an overview of SNAREopathies, with a focus in this post on SNAP25 and VAMP2.
Expanding clinical actionability in GLUT1 Deficiency through a blood-based biomarker
GLUT1DS. Disease-causing variants in SLC2A1 are associated with a rare genetic neurometabolic condition known as GLUT1 Deficiency Syndrome (GLUT1DS). While GLUT1DS is typically diagnosed through molecular genetic testing, the diagnostic strategy in some cases includes lumbar puncture to measure cerebrospinal fluid (CSF) glucose to confirm the diagnosis. In a recent study, Mochel and collaborators performed a multicenter validation study of a blood-based biomarker for GLUT1DS. Here is a brief review on their publication and the utility of molecular biomarkers in GLUT1DS and genetic epilepsies more broadly.
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.
Ring Chromosome 20 – here is what you need to know in 2023
Ring chromosome 20. If you are a regular reader of this blog, you’ll know that much of our focus is on single genes and their relationships to neurodevelopmental disorder. Admittedly, we may neglect cytogenetic conditions. However, in today’s post, we highlight ring chromosome 20 as a likely underdiagnosed genetic epilepsy with distinct clinical features.
CLTC: The neurological backpacker of intracellular transport
Shouldering the Load. The CLTC gene encodes the protein clathrin, which plays a crucial role in the formation of clathrin-coated vesicles, responsible for transporting proteins and other molecules within neurons. Clathrin-mediated endocytosis is also a crucial process for the recycling of synaptic vesicles in neurons, enabling efficient neurotransmitter release and synaptic transmission. The discovery of CLTC-related disorders has revealed a diverse spectrum of neurological conditions, ranging from intellectual disability to epilepsy. Here is a blog post on CLTC-related disorders as the forgotten disease of synaptic vesicle recycling, highlighting the crucial role of clathrin in maintaining proper neurological function.
Revisiting the genetics of cerebral palsy
CP. Over the last few years, a range of high-impact publications have revolutionized our understanding of the genetics of cerebral palsy (CP). While CP is traditionally thought of as an exclusively acquired disorder, massive parallel sequencing studies have suggested causative genetic etiologies in up to 30% of individuals. Here is an overview of the emerging genetics of CP through the lens of neurodevelopmental disorders, questioning some of the assumptions that are typically made when comparing both disease groups. Continue reading
Five things to know about SLC6A1 in 2023
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.
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
