A Korean Family with Arg1448Cys Mutation of SCN4A Channel Causing Paramyotonia Congenita: Electrophysiologic, Histopathologic, and Molecular Genetic Studies

Kim, Dae Seong; Kim, Eun Joo; Jung, Dae Soo; Park, Kyu Hyun; Kim, In Joo; Kwak, Ki Young; Kim, Cheol Min; Ko, Hyun-Yoon

doi:10.3346/jkms.2002.17.6.856

Cited by 9 publications

(11 citation statements)

References 14 publications

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“…To date, there are only a few reports of surface-recorded repetitive firing in myotonic disorders. 13,14 Interestingly, these myotonic discharges occurred in all PC patients with T1313M or R1448C mutations and only in one-third of MC patients. Such postexercise surface-recorded myotonic activity was ob-…”

Section: A Novel Electromyographic Sign Of Myotonia: Postexercise Myomentioning

confidence: 99%

Electromyography guides toward subgroups of mutations in muscle channelopathies

Fournier

Arzel

Sternberg

et al. 2004

Annals of Neurology

264

310

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Myotonic syndromes and periodic paralyses are rare disorders of skeletal muscle characterized mainly by muscle stiffness or episodic attacks of weakness. Familial forms are caused by mutations in genes coding for skeletal muscle voltage-gated ion channels. Exercise is known to trigger, aggravate, or relieve the symptoms. Therefore, exercise can be used as a functional test in electromyography to improve the diagnosis of these muscle disorders. Abnormal changes in the compound muscle action potential can be disclosed using different exercise tests. We report the outcome of an inclusive electromyographic survey of a large population of patients with identified ion channel gene defects. Standardized protocols comprising short and long exercise tests were applied on 41 unaffected control subjects and on 51 case patients with chloride, sodium, or calcium channel mutations known to cause myotonia or periodic paralysis. These tests disclosed significant changes of compound muscle action potential, which generally matched the clinical symptoms. Combining the responses to the different tests defined five electromyographic patterns (I-V) that correlated with subgroups of mutations and may be used in clinical practice as guides for molecular diagnosis. We hypothesize that mutations are segregated into the different electromyographic patterns according to the underlying pathophysiological mechanisms.

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Section: A Novel Electromyographic Sign Of Myotonia: Postexercise Myomentioning

confidence: 99%

Electromyography guides toward subgroups of mutations in muscle channelopathies

Fournier

Arzel

Sternberg

et al. 2004

Annals of Neurology

264

310

View full text Add to dashboard Cite

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“…Not always but frequently PMC patients are found to be accompanied by Hyperkalemic periodic paralysis with increased level of serum creatine kinase. Voltagegated sodium channel a-subunit-encoding SCN4A genetic mutation is responsible for PMC (Kim et al 2002, Pereon et al 2003, where the cytoplasmic loop region between segment III and IV in sodium channel is hotspot for the mutation (McClatchey et al 1992;Ptacek et al 1992;Lerche et al 1993;Ptacek et al 1993;Sasaki et al 1999;Okuda et al 2001). It has also been studied that R1448H mutation causes cold-induced myotonia that leads to PMC and is responsible for slowed inactivation and faster recovery from inactivation as compared to non-mutant channels (Mohammadi et al 2003).…”

Section: Para Myotonia Congenita (Pmc)mentioning

confidence: 97%

Mutational Consequences of Aberrant Ion Channels in Neurological Disorders

2014

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Neurological channelopathies are attributed to aberrant ion channels affecting CNS, PNS, cardiac, and skeletal muscles. To maintain the homeostasis of excitable tissues, functional ion channels are necessary to rely electrical signals, whereas any malfunctioning serves as an intrinsic factor to develop neurological channelopathies. Molecular basis of these disease is studied based on genetic and biophysical approaches, e.g., loci positional cloning, whereas pathogenesis and bio-behavioral analysis revealed the dependency on genetic mutations and inter-current triggering factors. Although electrophysiological studies revealed the possible mechanisms of diseases, analytical study of ion channels remained unsettled and therefore underlying mechanism in channelopathies is necessary for better clinical application. Herein, we demonstrated (i) structural and functional role of various ion channels (Na(+), K(+), Ca(2+),Cl(-)), (ii) pathophysiology involved in the onset of their associated channelopathies, and (iii) comparative sequence and phylogenetic analysis of diversified sodium, potassium, calcium, and chloride ion channel subtypes.

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“…The R1448C SCN4A ‐mutation has been associated with a “pure” PMC or HyperPP phenotype . We report a Dutch patient in whom the R1448C mutation was associated with prolonged, severe attacks of weakness associated with hypokalemia and paramyotonia.…”

mentioning

confidence: 93%

“…In clinical practice, the co-occurrence of episodic weakness with paramyotonia helps to guide the clinician toward the diagnosis of HyperPP. 1 The R1448C SCN4A-mutation has been associated with a "pure" PMC [2][3][4][5] or HyperPP phenotype. [6][7][8] We report a Dutch patient in whom the R1448C mutation was associated with prolonged, severe attacks of weakness associated with hypokalemia and paramyotonia.…”

mentioning

confidence: 99%