The skeletal muscle chloride channel in dominant and recessive human myotonia

Science. 1992 Aug 7;257(5071):797-800. doi: 10.1126/science.1379744.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Southern
  • Chloride Channels
  • Chromosomes, Human, Pair 7*
  • Cloning, Molecular
  • DNA / genetics
  • Female
  • Genes, Dominant*
  • Genes, Recessive*
  • Genetic Linkage
  • Humans
  • Ion Channels / genetics*
  • Lod Score
  • Male
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Muscular Dystrophies / genetics*
  • Myotonia Congenita / genetics*
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • Receptors, Antigen, T-Cell / genetics
  • Recombination, Genetic
  • Sequence Homology, Nucleic Acid

Substances

  • Chloride Channels
  • Ion Channels
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • DNA

Associated data

  • GENBANK/M97820