ArticleProceedings of the National Academy of Sciences of the United States of America2003
Myasthenic syndrome caused by mutation of the SCN4A sodium channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.
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Who cites it
77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Myotonia: Recognition, Evaluation, and Differential Diagnosis.Muscle & nerve · 2026Review
- Review
- Genome-wide selection and association analyses implicate retinal and reproductive genes in laying-period variation of domestic geese.Poultry science · 2026Article
- Molecular genetics of skeletal muscle channelopathies.Journal of human genetics · 2025Review
- Review of 40 genes causing congenital myasthenic syndromes.Journal of human genetics · 2025Review
- Novel SCN4A Variants Associated With Myalgic Myotonic Disorder or Paramyotonia.European journal of neurology · 2025Article
- Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants.Journal of human genetics · 2025Article
- Spatial transcriptomics in embryonic mouse diaphragm muscle reveals regional gradients and subdomains of developmental gene expression.iScience · 2024Article
- A retrospective study of accuracy and usefulness of electrophysiological exercise tests.Journal of neurology · 2024Article
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- Periodic paralysis.Handbook of clinical neurology · 2024Review
- The Importance of Early Treatment of Inherited Neuromuscular Conditions.Journal of neuromuscular diseases · 2024Review
- Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Excitability properties of mouse and human skeletal muscle fibres compared by muscle velocity recovery cycles.Neuromuscular disorders : NMD · 2022Article
- Case report: NovelFrontiers in pediatrics · 2022Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
In a myasthenic syndrome associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, nerve stimulation at physiologic rates rapidly decremented the compound muscle action potential. Intercostal muscle studies revealed no abnormality of the resting membrane potential, evoked quantal release, synaptic potentials, acetylcholine receptor channel kinetics, or endplate ultrastructure, but endplate potentials depolarizing the resting potential to -40 mV failed to excite action potentials. Pursuing this clue, we sequenced SCN4A encoding the skeletal muscle sodium channel (Nav1.4) and detected two heteroallelic mutations involving conserved residues not present in 400 normal alleles: S246L in the S4/S5 cytoplasmic linker in domain I, and V1442E in the S3/S4 extracellular linker in domain IV. The genetically engineered V1442E-Na channel expressed in HEK cells shows marked enhancement of fast inactivation close to the resting potential, and enhanced use-dependent inactivation on high-frequency stimulation; S246L is likely a benign polymorphism. The V1442E mutation in SCN4A defines a novel disease mechanism and a novel phenotype with myasthenic features.
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