The skeletal muscle chloride channel in dominant and recessive human myotonia.

Autosomal recessive generalized myotonia (Becker's disease) (GM) and autosomal dominant myotonia congenita (Thomsen's disease) (MC) are characterized by skeletal muscle stiffness that is a result of muscle membrane hyperexcitability. For both diseases, alterations in muscle chloride or sodium currents or both have been observed. A complementary DNA for a human skeletal muscle chloride channel (CLC-1) was cloned, physically localized on chromosome 7, and linked to the T cell receptor beta (TCRB) locus. Tight linkage of these two loci to GM and MC was found in German families. An unusual restriction site in the CLC-1 locus in two GM families identified a mutation associated with that disease, a phenylalanine-to-cysteine substitution in putative transmembrane domain D8. This suggests that different mutations in CLC-1 may cause dominant or recessive myotonia.