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. METHODS AND 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.
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. METHODS AND 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.
Authors: Cristina Dias; Murat Sincan; Praveen F Cherukuri; Rosemarie Rupps; Yan Huang; Hannah Briemberg; Kathryn Selby; James C Mullikin; Thomas C Markello; David R Adams; William A Gahl; Cornelius F Boerkoel Journal: Hum Mutat Date: 2012-02-28 Impact factor: 4.878
Authors: Marja W Wessels; Johanna C Herkert; Ingrid M Frohn-Mulder; Michiel Dalinghaus; Arthur van den Wijngaard; Ronald R de Krijger; Michelle Michels; Irenaeus Fm de Coo; Yvonne M Hoedemaekers; Dennis Dooijes Journal: Eur J Hum Genet Date: 2014-10-22 Impact factor: 4.246
Authors: Brian Lin; Suresh Govindan; Kyounghwan Lee; Piming Zhao; Renzhi Han; K Elisabeth Runte; Roger Craig; Bradley M Palmer; Sakthivel Sadayappan Journal: PLoS One Date: 2013-07-31 Impact factor: 3.240