Mutations in the SCN2A gene encoding a voltage-gated sodium channel Nav1.2 are associated with epilepsies, intellectual disability, and autism. SCN2A gain-of-function mutations cause early-onset severe epilepsies, while loss-of-function mutations cause autism with milder and/or later-onset epilepsies. Here we show that both heterozygous Scn2a-knockout and knock-in mice harboring a patient-derived nonsense mutation exhibit ethosuximide-sensitive absence-like seizures associated with spike-and-wave discharges at adult stages.
Read More» SCN2A Explained
Located on the long (q) arm of chromosome 2 at position 24.3 the SCN2A is sodium channel, voltage gated, type II alpha subunit. This gene has been identified to cause autism, epilepsy and other neurological issues like dystonia and dsyautonomia when there is a deletion or mutation of this gene.
Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability.SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channelsmakesSCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders.
Source: Progress in Understanding and Treating SCN2A-Mediated Disorders
» Basics of SCN2A
Dennis Lal, Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T. gives and overview about the current knowledge of SCN2A disorders in August 2017.
» Genetics & Physiology of SCN2A
SCN2A is one of the genes most commonly associated with early-onset epilepsy, and has recently been linked to autism spectrum disorder and developmental delay. SCN2A encodes a neuronal voltage gated sodium channel, NaV1.2 that is primarily found in excitatory neurons throughout the brain. In this webinar, Drs. Kevin Bender and Stephan Sanders will detail recent advances in our understanding of how different mutations in SCN2A contribute to the different forms of epilepsy, including benign infantile seizure and epileptic encephalopathy, and how these mutations contrast with those that contribute to autism. We will further discuss how the distribution of NaV1.2 within neurons develops over the first few years of life, and how these changes affect neuronal function. This development has important implications for understanding these disorders and in designing potential therapies in the future.
SCN2A Variant Browser Webinar Paper» SCN2A Resources
Map Your SCN2A Variant
This visual tool allows you to populate the SCN2A protein or nucleotide change inorder to map where the location of the variant is on the gene.
Create YoursSCN2A Printable Brochure
The FamilieSCN2A printable and downloadable brochure.
Download PDF FileFamilieSCN2A Resources
FamilieSCNA Foundation has put together a Live Binder of resources which include articles, information on diagnosis related to SCN2A, blog site and more. We update Live Binder with information that is posted in our private FaceBook group, as well as in our newsletters.
Click HereJoin Us On Facebook
Did you or your child just receive a new diagnosis of SCN2A? If so, please know you are not alone!
If you are a Facebook users please join us on our private Facebook page where you can virtually connect with other parents and caregivers of children with SCN2A. Once you have been added to the group, we ask you post your child's specific variant. This helps others see if their child has the same diagnosis as yours and also allows us to collect data for further research in the hope to find a cure.
Let's Get SocialCurrent Research
If you are interested in participating in research to help find treatments and a cure for SCN2A, please review the current research projects. These projects help get us closer to understanding this complex sodium ion channel disorder and closer to improving treatments and finding a cure. Participation is completely voluntary for anyone who has been diagnosed with a change in their SCN2A gene.
View ResearchPut Your Child On The Map
As the parent of a child with an SCN2A mutation, we ask that you please put yourself and your child "on the map" by reaching out and letting us know you exist (even anonymously, if you prefer). It is one of THE MOST IMPORTANT THINGS YOU CAN DO FOR YOUR CHILD, and it is the only way we will ever be able to advocate for new SCN2A treatments and therapies.
Register Your Child» SCN2A Publications
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The splicing of pre-mRNAs into mature transcripts is remarkable for its precision, but the mechanisms by which the cellular machinery achieves such specificity are incompletely understood. Here, we describe a deep neural network that accurately predicts splice junctions from an arbitrary pre-mRNA transcript sequence, enabling precise prediction of noncoding genetic variants that cause cryptic splicing.
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Efforts to identify the causes of autism spectrum disorders have highlighted the importance of both genetics and environment, but the lack of human models for many of these disorders limits researchers’ attempts to understand the mechanisms of disease and to develop new treatments. Induced pluripotent stem cells offer the opportunity to study specific genetic and environmental risk factors, but the heterogeneity of donor genetics may obscure important findings.
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The efficacy of valproic acid (VPA) varies widely in clinical treatment of epileptic patients. Our study is aimed at exploring a potential association between polymorphisms of SCN1A, SCN2A, and UGT2B7 genetic factors and VPA responses. Methods. In this observational study, a total of 114 epileptic patients only treated with VPA for at least 1 year were included to explore the genetic polymorphisms of drug responses (mean follow-up time: 3:68 ± 1:78 years).
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On August 2–3, 2019, the FamilieSCN2A Foundation held their biennial SCN2A Professional and Family meeting, in Seattle, Washington. The gathering brought together 37 families of individuals with mutations in the SCN2A gene, 60 investigators, eight clinicians and five industry groups that conduct research and/or clinical work on conditions related to this genetic change. A number of SFARI scientists and staff also attended the event.
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Clinical exome sequencing is frequently used to identify gene-disrupting variants in individuals with neurodevelopmental disorders. While splice-disrupting variants are known to contribute to these disorders, clinical interpretation of cryptic splice variants outside of the canonical splice site has been challenging. Here, we discuss papers that improve such detection.
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SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain
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We identified a novel de novo SCN2A variant (M1879T) associated with infantile-onset epilepsy that responded dramatically to sodium channel blocker antiepileptic drugs. We analyzed the functional and pharmacological consequences of this variant to establish pathogenicity, and to correlate genotype with phenotype and clinical drug response.
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Alternative splicing potentiates dysfunction of early-onset epileptic encephalopathy SCN2A variants
- Posted on Journal of General Physiology |
- Jan 29, 2020
Epileptic encephalopathies are severe forms of infantile-onset epilepsy often complicated by severe neurodevelopmental impairments. Some forms of early-onset epileptic encephalopathy (EOEE) have been associated with variants in SCN2A, which encodes the brain voltage-gated sodium channel NaV1.2.
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PROGRESS IN UNDERSTANDING & TREATING SCN2A-MEDIATED DISORDERS
- Published in Trends in Neurosciences |
- Apr 22, 2018
Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, andintellectual disability.SCN2Aencodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms.
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SCN2A in benign seizures, autism and epileptic encephalopathy
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SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain
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SCN2a: This is what you need to know A 2016 UPDATE
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BRAIN a journal of neurology published 2017: SCN2A: phenotypes and treatment
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