Referenced in: none

Automatically associated channels: ClC1 , ClC4 , Nav1.5

Title: Myotonia caused by mutations in the muscle chloride channel gene CLCN1.

Authors: Michael Pusch

Journal, date & volume: Hum. Mutat., 2002 Apr , 19, 423-34

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11933197

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.