- •We identified a SCN4A mutation (p.L703P) in a Chinese family with non-dystrophic myotonias (NDM).
- •Characterization of mutant channel revealed both gain-of-function and loss-of-function changes in gating properties.
- •Literature search results in two independent case reports of NDM patients carrying L703P mutation in Nav1.4 channels.
- •The L703P is a recurrent mutation associated with NDM.
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- Targeted therapies for skeletal muscle ion channelopathies: systematic review and steps towards precision medicine.J Neuromuscul. 2021; 8: 357-381https://doi.org/10.3233/JND-200582
- An up-to-date overview of the complexity of genotype-phenotype relationships in myotonic channelopathies.Front Neurol. 2020; 10: 1404https://doi.org/10.3389/fneur.2019.01404
- Prevalence study of genetically defined skeletal muscle channelopathies in England.Neurology. 2013; 80: 1472-1475https://doi.org/10.1212/WNL.0b013e31828cf8d0
- Skeletal muscle channelopathies: a guide to diagnosis and management.Pract Neurol. 2021; 21: 196-204https://doi.org/10.1136/practneurol-2020-002576
- Sodium channelopathies of skeletal muscle.Handb Exp Pharmacol. 2018; 246: 309-330https://doi.org/10.1007/164_2017_52
- Principles and standards for reporting animal experiments in the Journal of Physiology and Experimental Physiology.J. Physiol. (Lond.). 2015; 593: 2547-2549https://doi.org/10.1113/JP270818
- Electromyography guides toward subgroups of mutations in muscle channelopathies.Ann Neurol. 2004; 56: 650-661https://doi.org/10.1002/ana.20241
- Cold extends electromyography distinction between ion channel mutations causing myotonia.Ann Neurol. 2006; 60: 356-365https://doi.org/10.1002/ana.20905
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424https://doi.org/10.1038/gim.2015.30
- N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita.J. Physiol. (Lond.). 2017; 595: 6837-6850https://doi.org/10.1113/JP274877
- Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner.Mol Pain. 2018; 141744806918782229https://doi.org/10.1177/1744806918782229
- Clinical experience with long-term acetazolamide treatment in children with nondystrophic myotonias: a three-case report.Pediatr Neurol. 2014; 51: 537-541https://doi.org/10.1016/j.pediatrneurol
- A de novo mutation in the SCN4A gene causing sodium channel myotonia.J Neuromuscul Dis. 2015; 2: 181-184https://doi.org/10.3233/JND-150069
- Pharmacogenetics of myotonic hNav1.4 sodium channel variants situated near the fast inactivation gate.Pharmacol Res. 2019; 141: 224-235https://doi.org/10.1016/j.phrs.2019.01.004
- Recurrent and non-recurrent mutations of SCN8A in epileptic encephalopathy.Front Neurol. 2015; 6: 104https://doi.org/10.3389/fneur.2015.00104
- International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.Pharmacol Rev. 2005; 57: 397-409https://doi.org/10.1124/pr.57.4.4
- Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta1.Science. 2018; 362: eaau2486https://doi.org/10.1126/science.aau2486
- Na channels in skeletal muscle concentrated near the neuromuscular junction.Nature. 1985; 313: 588-590https://doi.org/10.1038/313588a0
- Sodium channel myotonia and a novel Gly701Asp mutation in the SCN4A gene: from an ophthalmological symptom to a familial disease.Neuroophthalmology. 2020; 45: 41-44https://doi.org/10.1080/01658107.2020.1779316
- Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.J Neurol Neurosurg Psychiatry. 2003; 74: 1339-1341https://doi.org/10.1136/jnnp.74.9.1339
- Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.J Neurol Neurosurg Psychiatry. 2001; 70: 618-623https://doi.org/10.1136/jnnp.70.5.618
- Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation.J Neurosci. 1999; 19: 4762-4771https://doi.org/10.1523/JNEUROSCI.19-12-04762.1999
- Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.Brain. 2016; 139: 674-691https://doi.org/10.1093/brain/awv352
- Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome.Ann Neurol. 2015; 77: 840-850https://doi.org/10.1002/ana.24389
- A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.Neurology. 2016; 86: 161-169https://doi.org/10.1212/WNL.0000000000002264
- When all is lost...a severe myopathy with hypotonia from sodium channel mutations.Brain. 2016; 139: 642-644https://doi.org/10.1093/brain/awv400
- Sodium channel slow inactivation as a therapeutic target for myotonia congenita.Ann Neurol. 2015; 77: 320-332https://doi.org/10.1002/ana.24331
- Enhanced slow inactivation by V445M: a sodium channel mutation associated with myotonia.Biophys J. 1999; 76: 861-868https://doi.org/10.1016/S0006-3495(99)77249-8
- Slow inactivation of the NaV1.4 sodium channel in mammalian cells is impeded by co-expression of the beta1 subunit.Pflugers Arch. 2009; 457: 1253-1263https://doi.org/10.1007/s00424-008-0600-8
- Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy.J Clin Neurol. 2009; 5: 186-191https://doi.org/10.3988/jcn.2009.5.4.186