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Updated: Sep 12, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Molecular genetics of skeletal muscle channelopathies
Tomoya Kubota1, Masanori P Takahashi2,3
1Department of Clinical Laboratory and Biomedical Sciences, Division of Health Sciences, Graduate School of Medicine, The University of Osaka, Osaka, Japan. tomoya-k@sahs.med.osaka-u.ac.jp.
Abstract:
Skeletal muscle channelopathies are genetic disorders associated with variants in genes encoding ion channels and related proteins expressed in skeletal muscle. Most commonly, these involve genes encoding voltage-gated ion channels (VGICs) that regulate sarcolemmal excitability, including CLCN1 for ClC-1, SCN4A for the Nav1.4 α subunit, CACNA1S for the Cav1.1 α subunit, and KCNJ2 for Kir2.1. Skeletal muscle channelopathies primarily manifest with two clinical symptoms: myotonia, characterized by delayed muscle relaxation, and paralysis and classified into two disease types: non-dystrophic myotonia and periodic paralysis. Recent advances in the clinical application of next-generation sequencing have improved diagnostic rate and provided epidemiological evidence of the diseases. Furthermore, atypical phenotypes have been identified, indicating that skeletal muscle channelopathies present a broad clinical spectrum. This review provides an updated overview of the clinical and genetic aspects of skeletal muscle channelopathies and discusses key issues that require further investigation.
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