ArticleCommunications biology2022
Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Mechanisms of SCN2A loss of function do not predict presence or phenotype of epilepsy.Epilepsia · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Review
- Development and Adaptive Function in Individuals WithNeurology · 2025Article
- Antisense oligonucleotide treatment in a preterm infant with early-onset SCN2A developmental and epileptic encephalopathy.Nature medicine · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Rare dysfunctional SCN2A variants are associated with malformation of cortical development.Epilepsia · 2025Article
- International Precision Child Health Partnership (IPCHiP): an initiative to accelerate discovery and improve outcomes in rare pediatric disease.NPJ genomic medicine · 2025Review
- Assessing Communication Impairments in a Rare Neurodevelopmental Disorder: TheNeurology. Clinical practice · 2025Article
- Genetic crosstalk of autism spectrum disorders and epilepsy: an insight into the presynapse.Frontiers in neurology · 2025Article
- DecipheringArXiv · 2024Article
- Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions.Nature communications · 2024Article
- Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders.Brain : a journal of neurology · 2024Article
- Molecular and cellular context influences SCN8A variant function.JCI insight · 2024Article
- Opto-electronic feedback control of membrane potential for real-time control of action potentials.Cell reports methods · 2023Article
- Scn2a insufficiency alters spontaneous neuronal CaiScience · 2023Article
- Distinguishing Loss-of-Function and Gain-of-FunctionNeurology. Genetics · 2023Article
- Predicting functional effects of ion channel variants using new phenotypic machine learning methods.PLoS computational biology · 2023Article
- Evaluating the interplay between estrous cyclicity and flurothyl-induced seizure susceptibility inmicroPublication biology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 12 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In SCN2A-related disorders, there is an urgent demand to establish efficient methods for determining the gain- (GoF) or loss-of-function (LoF) character of variants, to identify suitable candidates for precision therapies. Here we classify clinical phenotypes of 179 individuals with 38 recurrent SCN2A variants as early-infantile or later-onset epilepsy, or intellectual disability/autism spectrum disorder (ID/ASD) and assess the functional impact of 13 variants using dynamic action potential clamp (DAPC) and voltage clamp. Results show that 36/38 variants are associated with only one phenotypic group (30 early-infantile, 5 later-onset, 1 ID/ASD). Unexpectedly, we revealed major differences in outcome severity between individuals with the same variant for 40% of early-infantile variants studied. DAPC was superior to voltage clamp in predicting the impact of mutations on neuronal excitability and confirmed GoF produces early-infantile phenotypes and LoF later-onset phenotypes. For one early-infantile variant, the co-expression of the α
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.