Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle

Nat Genet. 1996 May;13(1):63-9. doi: 10.1038/ng0596-63.


The muscle myosins and hexomeric proteins consisting of two heavy chains and two pairs of light chains, the latter called essential (ELC) and regulatory (RLC). The light chains stabilize the long alpha helical neck of the myosin head. Their function in striated muscle, however, is only partially understood. We report here the identification of distinct missense mutations in a skeletal/ventricular ELC and RLC, each of which are associated with a rare variant of cardiac hypertrophy as well as abnormal skeletal muscle. We show that myosin containing the mutant ELC has abnormal function, map the mutant residues on the three-dimensional structure of myosin and suggest that the mutations disrupt the stretch activation response of the cardiac papillary muscles.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / metabolism
  • Chickens
  • DNA Primers
  • Female
  • Genetic Linkage
  • Humans
  • Lod Score
  • Male
  • Mice
  • Models, Structural
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism*
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism
  • Myocardium / metabolism*
  • Myosin Light Chains / chemistry
  • Myosin Light Chains / genetics*
  • Myosins / chemistry*
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational*
  • Protein Structure, Secondary
  • Rats
  • Sequence Homology, Amino Acid
  • Ventricular Dysfunction, Left


  • DNA Primers
  • Myosin Light Chains
  • Myosins