J Korean Med Sci.  2009 Dec;24(6):1038-1044. 10.3346/jkms.2009.24.6.1038.

Novel CLCN1 Mutations and Clinical Features of Korean Patients with Myotonia Congenita

• Moon IS
• Kim HS
• Shin JH
• Park YE
• Park KH
• Shin YB
• Bae JS
• Choi YC
• Kim DS

• KMID: 1783130
• DOI: http://doi.org/10.3346/jkms.2009.24.6.1038

Abstract

Myotonia congenita (MC) is a form of nondystrophic myotonia caused by a mutation of CLCN1, which encodes human skeletal muscle chloride channel (CLC-1). We performed sequence analysis of all coding regions of CLCN1 in patients clinically diagnosed with MC, and identified 10 unrelated Korean patients harboring mutations. Detailed clinical analysis was performed in these patients to identify their clinical characteristics in relation to their genotypes. The CLCN1 mutational analyses revealed nine different point mutations. Of these, six (p.M128I, p.S189C, p.M373L, p.P480S, p.G523D, and p.M609K) were novel and could be unique among Koreans. While some features including predominant lower extremity involvement and normal to slightly elevated creatine kinase levels were consistently observed, general clinical features were highly variable in terms of age of onset, clinical severity, aggravating factors, and response to treatment. Our study is the first systematic study of MC in Korea, and shows its expanding clinical and genetic spectrums.

Keyword

Myotonia Congenita; CLCN1; Clinical Features

MeSH Terms

Adult
Amino Acid Sequence
Asian Continental Ancestry Group/*genetics
Base Sequence
Child, Preschool
Chloride Channels/*genetics
DNA Mutational Analysis
Exons
Humans
Infant
Korea
Male
Molecular Sequence Data
Myotonia Congenita/*genetics
*Point Mutation
Protein Conformation
Young Adult

Figure

• 

  Fig. 1 Chromatograms of novel mutations identified in the study. (A) c.384G>A (p.M128I), (B) c.566C>G (p.S189C), (C) c.1117A>T (p.M373L), (D) c.1438C>T (p.480S), (E) c.1568G>A (p.G523D), (F) c.1826T>A (p.M609K).

• 

  Fig. 2 Two-dimensional representation of the structure of a CLC subunit (9) showing the locations of mutations identified in this study.

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