title: Expression patterns of cardiac myofilament proteins: genomic and protein analysis of surgical myectomy tissue from patients with obstructive hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Mutations in myofilament proteins, most commonly MYBPC3-encoded myosin-binding protein C and MYH7-encoded beta-myosin heavy chain, can cause hypertrophic cardiomyopathy (HCM). Despite significant advances in structure-function relationships pertaining to the cardiac sarcomere, there is limited knowledge of how a mutation leads to clinical HCM. We, therefore, set out to study expression and localization of myofilament proteins in left ventricular tissue of patients with HCM.
  
  
  RESULTS
  Frozen surgical myectomy specimens from 47 patients with HCM were examined and genotyped for mutations involving 8 myofilament-encoding genes. Myofilament protein levels were quantified by Western blotting with localization graded from immunohistochemical staining of tissue sections. Overall, 25 of 47 (53%) patients had myofilament-HCM, including 12 with MYBPC3-HCM and 9 with MYH7-HCM. As compared with healthy heart tissue, levels of myofilament proteins were increased in patients manifesting a mutation in either gene. Patients with a frameshift mutation predicted to truncate MYBPC3 exhibited marked disturbances in protein localization as compared with missense mutations in either MYBPC3 or MYH7.
  
  
  CONCLUSIONS
  In this first expression study in human HCM tissue, increased myofilament protein levels in patients with either MYBPC3- or MYH7-mediated HCM suggest a poison peptide mechanism. Specifically, the mechanism of dysfunction may vary according to the genetic subgroup suggested by a distinctly abnormal distribution of myofilament proteins in patients manifesting a truncation mutation in MYBPC3.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Medicine/Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jeanne L
authors.initials: JL
authors.lastname: Theis
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Bos
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.forename: Dylan V
authors.initials: DV
authors.lastname: Miller
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Dearani
authors.forename: Hartzell V
authors.initials: HV
authors.lastname: Schaff
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Steve R
authors.initials: SR
authors.lastname: Ommen
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human