ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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90 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- Genetic polymorphisms in SCN2A are not associated with epilepsy risk and AEDs response: evidence from a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Functional and pharmacological characterization of theEpilepsy & behavior reports · 2026Article
- Nonsense-mediated decay influences position-dependent effects of SCN2A premature stop codons on neuronal excitability and behavior.Molecular psychiatry · 2026Article
- Review
- Generation and characterization of human-induced pluripotent stem cell lines from patients with autism spectrum disorder and SCN2A variants.Human cell · 2025Article
- A novel KDM5C mutation associated with intellectual disability: molecular mechanisms and clinical implications.Italian journal of pediatrics · 2025Article
- DecipheringArXiv · 2024Article
- An Inducible Luminescent System to Explore Parkinson's Disease-Associated Genes.International journal of molecular sciences · 2024Article
- Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Inversed Effects of Nav1.2 Deficiency at Medial Prefrontal Cortex and Ventral Tegmental Area for Prepulse Inhibition in Acoustic Startle Response.Molecular neurobiology · 2024Article
- Article
- Canadian Regulatory Framework and Regulatory Requirements for Cell and Gene Therapy Products.Advances in experimental medicine and biology · 2023Review
- Exploring the genetic etiology of drug-resistant epilepsy: incorporation of exome sequencing into practice.Acta neurologica Belgica · 2022Article
- Intragenic L1 Insertion: One Possibility of Brain Disorder.Life (Basel, Switzerland) · 2022Review
- Functional analysis of HECA variants identified in congenital heart disease in the Chinese population.Journal of clinical laboratory analysis · 2022Article
- Hyperexcitability and Pharmacological Responsiveness of Cortical Neurons Derived from Human iPSCs Carrying Epilepsy-Associated Sodium Channel Nav1.2-L1342P Genetic Variant.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Kv1.1 deficiency alters repetitive and social behaviors in mice and rescues autistic-like behaviors due to Scn2a haploinsufficiency.Brain and behavior · 2021Article
- Sodium channelopathies in neurodevelopmental disorders.Nature reviews. Neuroscience · 2021Review
- Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions.Frontiers in neurology · 2021Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations, exclusively missense, of voltage-gated sodium channel alpha subunit type 1 (SCN1A) and type 2 (SCN2A) genes were reported in patients with idiopathic epilepsy: generalized epilepsy with febrile seizures plus. Nonsense and frameshift mutations of SCN1A, by contrast, were identified in intractable epilepsy: severe myoclonic epilepsy in infancy (SMEI). Here we describe a first nonsense mutation of SCN2A in a patient with intractable epilepsy and severe mental decline. The phenotype is similar to SMEI but distinct because of partial epilepsy, delayed onset (1 year 7 months), and absence of temperature sensitivity. A mutational analysis revealed that the patient had a heterozygous de novo nonsense mutation R102X of SCN2A. Patch-clamp analysis of Na(v)1.2 wild-type channels and the R102X mutant protein coexpressed in human embryonic kidney 293 cells showed that the truncated mutant protein shifted the voltage dependence of inactivation of wild-type channels in the hyperpolarizing direction. Analysis of the subcellular localization of R102X truncated protein suggested that its dominant negative effect could arise from direct or indirect cytoskeletal interactions of the mutant protein. Haploinsufficiency of Na(v)1.2 protein is one plausible explanation for the pathology of this patient; however, our biophysical findings suggest that the R102X truncated protein exerts a dominant negative effect leading to the patient's intractable epilepsy.
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