ClinVar

In a female infant with fatal cardiomyopathy (CMH4; 115197) who also had evidence of skeletal myopathy, Tajsharghi et al. (2010) identified homozygosity for a 2827C-T transition, resulting in an arg943-to-ter (R943X) substitution in the MYBPC3 gene. Skeletal muscle biopsy at 2 months of age showed pronounced myopathic changes with numerous small fibers, which all expressed slow/beta-cardiac myosin heavy chain protein (MYH7; 160760). Electron microscopy revealed disorganization of the sarcomeres and partial depletion of thick filaments in the small fibers; immunohistochemical staining showed the presence of cardiac MYBPC in the small abnormal fibers. RT-PCR and sequencing demonstrated the mutation in transcripts of skeletal muscle. Tajsharghi et al. (2010) noted that cardiac MYBPC is not normally expressed in skeletal muscle, and stated that the reason for the ectopic expression of cardiac MYBPC remained unknown. The R943X mutation had previously been identified in compound heterozygosity with other truncating MYBPC3 mutations in 2 unrelated Dutch infants with fatal hypertrophic cardiomyopathy (Lekanne Deprez et al., 2006); skeletal myopathy was not mentioned in that report.