ArticleBrain : a journal of neurology2014
Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis.
Article in Brain : a journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Review
- Molecular genetics of skeletal muscle channelopathies.Journal of human genetics · 2025Review
- Pharmacological therapy of non-dystrophic myotonias.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- MyoV: a deep learning-based tool for the automated quantification of muscle fibers.Briefings in bioinformatics · 2024Article
- Periodic paralysis across the life course: age-related phenotype transition and sarcopenia overlap.Frontiers in neurology · 2024Review
- A c.1775C > T Point Mutation of Sodium Channel Alfa Subunit Gene (SCN4A) in a Three-Generation Sardinian Family with Sodium Channel Myotonia.Journal of neuromuscular diseases · 2024Article
- Excitability properties of mouse and human skeletal muscle fibres compared by muscle velocity recovery cycles.Neuromuscular disorders : NMD · 2022Article
- Hypokalaemic periodic paralysis and myotonia in a patient with homozygous mutation p.R1451L in NaScientific reports · 2018Article
- A genetic modifier suggests that endurance exercise exacerbates Huntington's disease.Human molecular genetics · 2018Article
- Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.Lancet (London, England) · 2018Article
- Sodium Channelopathies of Skeletal Muscle.Handbook of experimental pharmacology · 2018Review
- Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.Protein & cell · 2017Review
- Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.Brain : a journal of neurology · 2016Article
- Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration.Human molecular genetics · 2016Article
- Physiological basis for muscle stiffness and weakness in a knock-in M1592V mouse model of hyperkalemic periodic paralysis.Physiological reports · 2015Article
- Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels.Frontiers in physiology · 2015Review
- Ageing contributes to phenotype transition in a mouse model of periodic paralysis.JCSM rapid communicationsArticle
Corrections and comments
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Authors and funding
29 authors at 9 institutions in 3 countries.
Funding
Abstract
Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target.
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Registered trials
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.