title: Myotonia caused by mutations in the muscle chloride channel gene CLCN1.
abstract: Pure non-syndromic, non-dystrophic myotonia in humans is caused by mutations in the genes coding for the skeletal muscle sodium channel (SCN5A) or the skeletal muscle chloride channel (CLCN1) with similar phenotypes. Chloride-channel myotonia can be dominant (Thomsen-type myotonia) or recessive (Becker-type myotonia). More than 60 myotonia-causing mutations in the CLCN1 gene have been identified, with only a few of them being dominant. A common phenotype of dominant mutations is a dominant negative effect of mutant subunits in mutant-WT heterodimers, causing a large shift of the steady-state open probability voltage-dependence towards more positive, unphysiological voltages. The study of the properties of disease causing mutations has helped in understanding the functional properties of the CLC-1 channel that is part of a nine-member gene family of chloride channels. The large body of knowledge obtained for CLC-1 may also help to better understand the other CLC channels, three of which are also involved in genetic diseases.
authors.affiliation: Istituto di Cibernetica e Biofisica, CNR, Genova, Italy. pusch@barolo.icb.ge.cnr.it
authors.forename: Michael
authors.initials: M
authors.lastname: Pusch
mesh_terms: D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019281:Dimerization; D005091:Exons / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D009132:Muscles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009222:Myotonia / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D021122:Protein Subunits