Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy

Sang Chan Lee, Hyang Sook Kim, Yeong Eun Park, Youngchul Choi, Kyu yun Park, Dae Seong Kim

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background and Purpose Mutations of the skeletal muscle sodium channel gene SCN4A,which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenital (PMC), potassium-ggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. Methods Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. Results We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure yotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. Conclusions Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.

Original languageEnglish
Pages (from-to)186-191
Number of pages6
JournalJournal of Clinical Neurology (Korea)
Volume5
Issue number4
DOIs
Publication statusPublished - 2009 Jan 1

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Channelopathies
Skeletal Muscle
Sodium
Mutation
Myotonia Congenita
Myotonia
Hyperkalemic Periodic Paralysis
Hypokalemic Periodic Paralysis
Congenital Myasthenic Syndromes
Sodium Channels
Missense Mutation
Paralysis
Genes
Sequence Analysis
Potassium
Differential Diagnosis
Chromosomes
Phenotype
DNA

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Lee, Sang Chan ; Kim, Hyang Sook ; Park, Yeong Eun ; Choi, Youngchul ; Park, Kyu yun ; Kim, Dae Seong. / Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy. In: Journal of Clinical Neurology (Korea). 2009 ; Vol. 5, No. 4. pp. 186-191.
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Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy. / Lee, Sang Chan; Kim, Hyang Sook; Park, Yeong Eun; Choi, Youngchul; Park, Kyu yun; Kim, Dae Seong.

In: Journal of Clinical Neurology (Korea), Vol. 5, No. 4, 01.01.2009, p. 186-191.

Research output: Contribution to journalArticle

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N2 - Background and Purpose Mutations of the skeletal muscle sodium channel gene SCN4A,which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenital (PMC), potassium-ggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. Methods Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. Results We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure yotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. Conclusions Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.

AB - Background and Purpose Mutations of the skeletal muscle sodium channel gene SCN4A,which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenital (PMC), potassium-ggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. Methods Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. Results We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure yotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. Conclusions Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.

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