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.
Tajsharghi
Homa
H
Department of Pathology, Neuromuscular Center, Sahlgrenska University Hospital, Göteborg, Sweden.
Thornell
Lars-Eric
LE
Lindberg
Christopher
C
Lindvall
Björn
B
Henriksson
Karl-Gösta
KG
Oldfors
Anders
A
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000368:Aged; D001120:Arginine / Q000235:genetics; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms; D016415:Sequence Alignment; D013194:Staining and Labeling; D014364:Tryptophan / Q000235:genetics
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D020033:Protein Isoforms; D014364:Tryptophan; D001120:Arginine; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains