Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency*

Circulation Research

Volumn 105, Issue 3, 2009, Pages 219-222

  Marston, Steven ^a   Copeland, O'Neal ^a   Jacques, Adam ^a   Livesey, Karen ^b   Tsang, Victor ^c,d   McKenna, William J ^c,d   Jalilzadeh, Shapour ^e,f   Carballo, Sebastian ^e,f   Redwood, Charles ^e,f   Watkins, Hugh ^e,f  

^a Cardiovascular Science

^b NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^c CHURCHILL HOSPITAL   (United Kingdom)

^d Institute of Cardiovascular Science

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

^f UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Cardiomyopathy; Mutation; Myocardial contractility

Indexed keywords

MESSENGER RNA; MYOSIN BINDING PROTEIN C; CARRIER PROTEIN; MYOSIN-BINDING PROTEIN C;

ALLELE; ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; GENE MUTATION; HEART LEFT VENTRICLE; HOMOGENATE; HUMAN; HUMAN TISSUE; HYPERTROPHIC CARDIOMYOPATHY; IMMUNOBLOTTING; MISSENSE MUTATION; MUSCLE FIBRIL; MUSCLE RESECTION; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; CASE CONTROL STUDY; GENETICS; GENOTYPE; HAPLOIDY; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE; HEART VENTRICLE; METABOLISM;

ALLELES; CARRIER PROTEINS; CASE-CONTROL STUDIES; GENOTYPE; HAPLOIDY; HEART VENTRICLES; HUMANS; HYPERTROPHY, LEFT VENTRICULAR; MUTATION, MISSENSE; MYOCARDIUM; RNA, MESSENGER;

EID: 69249236883     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.109.202440     Document Type: Article

References (18)

1. Flashman E, Redwood C, Moolman-Smook J, Watkins H. Cardiac myosin binding protein C: its role in physiology and disease. Circ Res. 2004;94:1279-1289.
2. Pohlmann L, Kroger I, Vignier N, Schlossarek S, Kramer E, Coirault C, Sultan KR, El-Armouche A, Winegrad S, Eschenhagen T, Carrier L. Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes. Circ Res. 2007;101:928-938.
3. Stelzer JE, Dunning SB, Moss RL. Ablation of cardiac myosin-binding protein-C accelerates stretch activation in murine skinned myocardium. Circ Res. 2006;98:1212-1218.
4. Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet. 1995;11:434-437.
5. Bonne G, Carrier L, Bercovici J, Cruaud C, Richard P, Hainque B, Gautel M, Labeit S, James M, Beckmann J, Weissenbach J, Vosberg HP, Fiszman M, Komajda M, Schwartz K. Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nat Genet. 1995;11:438-440.
6. Redwood CS, Moolman-Smook JC, Watkins H. Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy. Cardiovasc Res. 1999;44:20-36.
7. Rottbauer W, Gautel M, Zehelein J, Labeit S, Franz WM, Fischer C, Vollrath B, Mall G, Dietz R, Kubler W, Katus HA. Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization of cardiac transcript and protein. J Clin Invest. 1997;100:475-482.
8. Moolman JA, Reith S, Uhl K, Bailey S, Gautel M, Jeschke B, Fischer C, Ochs J, McKenna WJ, Klues H, Vosberg HP. A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance. Circulation. 2000;101:1396-1402.
9. van Dijk SJ, Dooijes D, dos Remedios C, Michels M, Lamers JM, Winegrad S, Schlossarek S, Carrier L, ten Cate FJ, Stienen GJ, van der Velden J. Cardiac myosin-binding protein C mutations and hypertrophic cardiomyopathy: haploinsufficiency, deranged phosphorylation, and cardiomyocyte dysfunction. Circulation. 2009;119:1473-1483.
10. Yang Q, Sanbe A, Osinska H, Hewett TE, Klevitsky R, Robbins J. A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy. J Clin Invest. 1998;102:1292-1300.
11. Yang Q, Sanbe A, Osinska H, Hewett TE, Klevitsky R, Robbins J. In vivo modeling of myosin binding protein C familial hypertrophic cardiomyopathy. Circ Res. 1999;85:841-847.
12. Carrier L, Knoll R, Vignier N, Keller DI, Bausero P, Prudhon B, Isnard R, Ambroisine ML, Fiszman M, Ross J Jr, Schwartz K, Chien KR. Asymmetric septal hypertrophy in heterozygous cMyBP-C null mice. Cardiovasc Res. 2004;63:293-304.
13. Harris SP, Bartley CR, Hacker TA, McDonald KS, Douglas PS, Greaser ML, Powers PA, Moss RL. Hypertrophic cardiomyopathy in cardiac myosin binding protein-C knockout mice. Circ Res. 2002;90:594-601.
14. Sarikas A, Carrier L, Schenke C, Doll D, Flavigny J, Lindenberg KS, Eschenhagen T, Zolk O. Impairment of the ubiquitin-proteasome system by truncated cardiac myosin binding protein C mutants. Cardiovasc Res. 2005;66:33-44.
15. Blanchard EM, Iizuka K, Christe M, Conner DA, Geisterfer-Lowrance A, Schoen FJ, Maughan DW, Seidman CE, Seidman JG. Targeted ablation of the murine alpha-tropomyosin gene. Circ Res. 1997;81:1005-1010.
16. Bahrudin U, Morisaki H, Morisaki T, Ninomiya H, Higaki K, Nanba E, Igawa O, Takashima S, Mizuta E, Miake J, Yamamoto Y, Shirayoshi Y, Kitakaze M, Carrier L, Hisatome I. Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation and associated with cardiac dysfunction in hypertrophic cardiomyopathy. J Mol Biol. 2008;384:896-907.
17. Hofmann PA, Hartzell HC, Moss RL. Alterations in Ca2- sensitive tension due to partial extraction of C-protein from rat skinned cardiac myocytes and rabbit skeletal muscle fibers. J Gen Physiol. 1991;97: 1141-1163.
18. Kulikovskaya I, McClellan G, Levine R, Winegrad S. Effect of extraction of myosin binding protein C on contractility of rat heart. Am J Physiol Heart Circ Physiol. 2003;285:H857-H865. (Pubitemid 36885920)