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An algorithm for candidate sequencing in non-dystrophic skeletal muscle channelopathies

Journal of Neurology volume 260, pages 1770–1777 (2013)Cite this article

Abstract

Human skeletal muscle channelopathies (HSMCs) are a group of heritable conditions with ion channel–related etiology and similar presentation. To create a comprehensive picture of the phenotypic spectrum for each condition and to devise a strategy that facilitates the differential diagnosis, we collected the genotype and phenotype information from more than 500 previously published HSMC studies. Using these records, we were able to identify clear correlations between particular clinical features and the underlying alteration(s) in the genes SCN4A, CACNA1S, KCNJ2, and CLCN1. This allowed us to develop a clinical, symptom-based, binary decision flow algorithm that predicts the proper genetic origin with high accuracy (0.88–0.93). The algorithm was implemented in a stand-alone online tool (“CGPS”—http://cgps.ddd.co.kr) to assist with HSCM diagnosis in the clinical practice. The CGPS provides simple, symptom-oriented navigation that guides the user to the most likely molecular basis of the presentation, which permits highly targeted genetic screens and, upon confirmation, tailored pharmacotherapy based on the molecular origin.

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Acknowledgments

This work was supported by a grant of the Korean Health Technology R and D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A100402).

Conflicts of interest

The authors declare that they have no conflict of interest.

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Affiliations

  1. Department of Neurology, The Brain Korea 21 Project, Chonnam National University Medical School, 8 Hakdong, Donggu, Gwangju, 501-757, Korea

    Tai-Seung Nam, Myeong-Kyu Kim & Kang-Ho Choi

  2. Department of Neurology, School of Medicine, University of California, Davis, 4635 Second Ave, Room 1004A, Sacramento, CA, 95817, USA

    Christoph Lossin

  3. Department of Neurology, Chosun University School of Medicine, Gwangju, Korea

    Dong-Uk Kim

  4. Department of Pediatrics, Chonnam National University Medical School, Gwangju, Korea

    Young-Ok Kim

  5. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Korea

    Seok-Yong Choi

  6. School of Electronics and Computer Engineering, Chonnam National University, Gwangju, Korea

    Sang-Cheol Park & In-Seop Na

Authors
  1. Tai-Seung Nam
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  2. Christoph Lossin
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  3. Dong-Uk Kim
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  4. Myeong-Kyu Kim
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Corresponding author

Correspondence to Myeong-Kyu Kim.

Additional information

T.-S. Nam and C. Lossin contributed equally to this work.

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Glossary

Glossary

CACNA1S :

Gene, calcium channel Cav1.1

CLCN1 :

Gene, human skeletal muscle chloride channel ClC-1

HSMC:

Human skeletal muscle channelopathy

Hyper-/Hypo-/NormoPP:

Hyper-/Hypo-/Normokalemic periodic paralysis

KCNJ2 :

Gene, inward-rectifier potassium ion channel Kir2.1

OMIM:

Online Mendelian Inheritance in Man (http://us-east.omim.org/)

PAM:

Potassium-aggravated myotonia

PMC:

Paramyotonia congenita

PubMed:

US National Library of Medicine (http://www.ncbi.nlm.nih.gov/pubmed/)

SCN4A :

Gene, human skeletal muscle sodium channel Nav1.4

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Nam, TS., Lossin, C., Kim, DU. et al. An algorithm for candidate sequencing in non-dystrophic skeletal muscle channelopathies. J Neurol 260, 1770–1777 (2013). https://doi.org/10.1007/s00415-013-6872-8

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  • DOI: https://doi.org/10.1007/s00415-013-6872-8

Keywords

  • Channelopathy
  • Skeletal muscle
  • Algorithm
  • Periodic paralysis
  • Myotonia