title: Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy, a familial myocardial condition caused by sarcomere protein mutations, is usually recognized by early adulthood. Hypertrophic cardiomyopathy of the elderly has similar clinical features but, notably, a later age of onset and noncontributory family history. Causes of elderly-onset hypertrophic cardiomyopathy are unknown.
  
  
  RESULTS
  Eighteen women and 13 men diagnosed with late-onset hypertrophic cardiomyopathy were studied. Initial symptoms occurred at 59.3 (+/-12.3) years, and diagnosis was made at 62.8 (+/-10.8) years. None had family histories of cardiomyopathy. Echocardiography demonstrated maximal left ventricular wall thickness of 19.9+/-3.8 mm, systolic anterior motion of the mitral valve (58%), and, in 11 individuals, left ventricular outflow tract gradients (average, 63+/-42.8 mm). Sarcomere protein gene analyses revealed 8 sequence variants in cardiac myosin binding protein-C (1 nonsense, 1 splice acceptor site, and 3 missense), cardiac troponin I (2 missense), and alpha-cardiac myosin heavy chain (1 missense). Seven variants were not found in over 170 normal chromosomes; 1 variant (cardiac myosin binding protein-C Arg326Gln) also occurred in a healthy adult.
  
  
  CONCLUSIONS
  Hypertrophic cardiomyopathy of the elderly can be a genetic disorder caused by dominant sarcomere protein mutations. The distribution of mutations in elderly-onset disease is strikingly different (P<0.00001) from that of familial, early onset hypertrophic cardiomyopathy. Whereas defects in beta-cardiac myosin heavy chain, cardiac troponin T, and alpha-tropomyosin account for > 45% of familial hypertrophic cardiomyopathy, none were found here. Rather, mutations in cardiac myosin binding protein-C, troponin I, and alpha-cardiac myosin heavy chain caused elderly-onset hypertrophic cardiomyopathy.
authors.affiliation: Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Niimura
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Patton
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Johann
authors.initials: J
authors.lastname: Soults
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Maron
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D004452:Echocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D012518:Sarcomeres / Q000235:genetics*; D016415:Sequence Alignment; D019210:Troponin I / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D009124:Muscle Proteins; D018995:Myosin Heavy Chains; D019210:Troponin I; D000099163:Myosin Binding Protein C