Myotonia caused by mutations in the muscle chloride channel gene CLCN1
Article first published online: 18 MAR 2002
Copyright © 2002 Wiley-Liss, Inc.
Volume 19, Issue 4, pages 423–434, April 2002
How to Cite
Pusch, M. (2002), Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum. Mutat., 19: 423–434. doi: 10.1002/humu.10063
- Issue published online: 18 MAR 2002
- Article first published online: 18 MAR 2002
- Telethon Italy. Grant Number: 1079
- myotonia congenita, generalized;
- skeletal muscle;
- chloride channel, voltage-gated;
- Thomsen disease;
- Becker disease
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. Hum Mutat 19:423–434, 2002. © 2002 Wiley-Liss, Inc.