Myosin binding protein-C (MyBP-C), a major
thick filament associated sarcomeric protein, plays an
important functional and structural role in regulating sarcomere
assembly and crossbridge formation. Missing or
aberrant MyBP-C proteins (both cardiac and skeletal) have
been shown to cause both cardiac and skeletal myopathies,
thereby emphasising its importance for the normal functioning
of the sarcomere. Mutations in cardiac MyBP-C are
a major cause of hypertrophic cardiomyopathy (HCM),
while mutations in skeletal MyBP-C have been implicated
in a disease of skeletal muscle—distal arthrogryposis type
1 (DA-1). Here we report the first detailed electron
microscopy studies on human cardiac and skeletal tissues
carrying MyBP-C gene mutations, using samples obtained
from HCM and DA-1 patients. We have used established
image averaging methods to identify and study the axial
distribution of MyBP-C on the thick filament by averaging
profile plots of the A-band of the sarcomere from electron
micrographs of human cardiac and skeletal myopathy
specimens. Due to the difficulty of obtaining normal human
tissue, we compared the distribution to the A-band structure
in normal frog skeletal, rat cardiac muscle and in
cardiac muscle of MyBP-C-deficient mice. Very similar
overall profile averages were obtained from the C-zones in
cardiac HCM samples and skeletal DA-1 samples with
MyBP-C gene mutations, suggesting that mutations in
MyBP-C do not