Nature Genetics
13, 63 - 69 (1996)
doi:10.1038/ng0596-63
Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscleKarl Poetter1, He Jiang2, Shahin Hassanzadeh1, Stephen R. Master3, Anthony Chang1, Marinos C. Dalakas4, Ivan Rayment5, James R. Sellers2, Lameh Fananapazir1
& Neal D. Epstein1, 6
1Inherited Cardiac Diseases Section, Room 7B/15, N.H.L.B.I., N.LH., Building 10, Bethesda, Maryland 20892-1650, USA
2Laboratory of Molecular Cardiology, N.H.L.B.I., N.I.H., Bethesda, Maryland 20892, USA
3Present address: Department of Molecular and Cellular Engineering, University of Pennsylvania Medical Center 308 Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, Pennsylvania 19104-6069, USA
4Neuromuscular Diseases Section, N.L.N.D.S., N.I.H., Bethesda, Maryland 20892, USA
5Departmentof Biochemistry and Institute for Enzyme Research, University of Wisconsin, Madison, Wisconsin 53705, USA
6e-mail: Nepstein@hocm.nhlbi.nih.gov The muscle myosins are 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.
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