Myosin storage myopathy associated with a heterozygous missense mutation in MYH7.

• Myosin constitutes the major part of the thick filaments in the contractile apparatus of striated muscle. MYH7 encodes the slow/beta-cardiac myosin heavy chain (MyHC), which is the main MyHC isoform in slow, oxidative, type 1 muscle fibers of skeletal muscle. It is also the major MyHC isoform of cardiac ventricles. Numerous missense mutations in the globular head of slow/beta-cardiac MyHC are associated with familial hypertrophic cardiomyopathy. We identified a missense mutation, Arg1845Trp, in the rod region of slow/beta-cardiac MyHC in patients with a skeletal myopathy from two different families. The myopathy was characterized by muscle weakness and wasting with onset in childhood and slow progression, but no overt cardiomyopathy. Slow, oxidative, type 1 muscle fibers showed large inclusions consisting of slow/beta-cardiac MyHC. The features were similar to a previously described entity: hyaline body myopathy. Our findings indicate that the mutated residue of slow/beta-cardiac MyHC is essential for the assembly of thick filaments in skeletal muscle. We propose the term myosin storage myopathy for this disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Adenosine Triphosphatases

metabolism

Aged

Arginine

genetics

Blotting

Western

DNA Mutational Analysis

Family Health

Female

Heterozygote

Humans

Immunohistochemistry

Male

Microscopy

Electron

Molecular Motor Proteins

Molecular Sequence Data

Muscle Fibers

Slow-Twitch

metabolism

ultrastructure

Muscular Diseases

genetics

metabolism

pathology

Mutation

Missense

Myosin Heavy Chains

genetics

metabolism

ultrastructure

Protein Isoforms

Sequence Alignment

Staining and Labeling

Tryptophan

genetics

Medical sciences

MEDICINE

Publikations- och innehållstyp

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