Unexpected myopathy associated with a mutation in MYBPC3 and misplacement of the cardiac myosin binding protein C.
BACKGROUND
Myosin binding protein C (MyBPC) is essential for the structure of the sarcomeres in striated muscle. There is one cardiac specific isoform and two skeletal muscle specific isoforms. Mutations in MYBPC3 encoding the cardiac isoform cause cardiomyopathy.


RESULTS
We have identified an infant with fatal cardiomyopathy due to a homozygous mutation, p.R943X, in MYBPC3. The patient also had an unexpected skeletal myopathy. The patient expressed the cardiac specific MyBPC isoform in skeletal muscle at transcript and protein levels. Numerous muscle fibres expressing the mutant cardiac isoform showed structural abnormalities with disorganisation of sarcomeres and depletion of myosin thick filaments.


CONCLUSIONS
The surprising identification of a skeletal myopathy in this patient was due to aberrant expression of mutant cardiac MyBPC in skeletal muscle.
Tajsharghi
Homa
H
Leren
Trond P
TP
Abdul-Hussein
Saba
S
Tulinius
Mar
M
Brunvand
Leif
L
Dahl
Hilde M
HM
Oldfors
Anders
A
D001483:Base Sequence; D009202:Cardiomyopathies / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C