title: The skeletal muscle chloride channel in dominant and recessive human myotonia.
abstract: 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.
authors.affiliation: Medical Center for Human Genetics, Marburg University, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Koch
authors.forename: K
authors.initials: K
authors.lastname: Steinmeyer
authors.forename: C
authors.initials: C
authors.lastname: Lorenz
authors.forename: K
authors.initials: K
authors.lastname: Ricker
authors.forename: F
authors.initials: F
authors.lastname: Wolf
authors.forename: M
authors.initials: M
authors.lastname: Otto
authors.forename: B
authors.initials: B
authors.lastname: Zoll
authors.forename: F
authors.initials: F
authors.lastname: Lehmann-Horn
authors.forename: K H
authors.initials: KH
authors.lastname: Grzeschik
authors.forename: T J
authors.initials: TJ
authors.lastname: Jentsch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D018118:Chloride Channels; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D004247:DNA