Cardiomyopathy: A systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations

Cardiology

Volumn 115, Issue 1, 2009, Pages 49-60

  Walsh, R ^a   Rutland, C ^b   Thomas, R ^a   Loughna, S ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

Beta myosin heavy chain; Cardiomyopathy; Hypertrophy, molecular basis; Mutation; Myosin heavy chain 7; Prognosis; Sarcomeric protein; Systematic review

Indexed keywords

AMINO ACID; MYOSIN HEAVY CHAIN; MYOSIN HEAVY CHAIN 7; UNCLASSIFIED DRUG;

AMINO ACID COMPOSITION; AMINO ACID SEQUENCE; CARDIOMYOPATHY; DISEASE SEVERITY; GENE; GENE LOCATION; HUMAN; MYH7 GENE; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SYSTEMATIC REVIEW;

CARDIAC MYOSINS; CARDIOMYOPATHIES; CODON, NONSENSE; GENOTYPE; HUMANS; MUTATION, MISSENSE; MYOSIN HEAVY CHAINS; PHENOTYPE; RNA SPLICE SITES;

EID: 70350393411     PISSN: 00086312     EISSN: None     Source Type: Journal    
DOI: 10.1159/000252808     Document Type: Review

References (85)

1. Fatkin D, Graham RM: Molecular mechanisms of inherited cardiomyopathies. Physiol Rev 2002; 82: 945-980.
2. Fananapazir L, Epstein ND: Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations. Circulation 1994; 89: 22-32.
3. Maron BJ, Roberts WC, Epstein SE: Sudden death in hypertrophic cardiomyopathy: a profile of 78 patients. Circulation 1982; 65: 1388-1394.
4. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P: Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 1996; 93: 841-842.
5. Van Driest SL, Jaeger MA, Ommen SR, Will ML, Gersh BJ, Tajik AJ, Ackerman MJ: Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 44: 602-610.
6. Karam S, Raboisson MJ, Ducreux C, Chalabreysse L, Millat G, Bozio A, Bouvagnet P: A de novo mutation of the beta cardiac myosin heavy chain gene in an infantile restrictive cardiomyopathy. Congenit Heart Dis 2008; 3: 138-143.
7. Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, Greutmann M, Hurlimann D, Yegitbasi M, Pons L, Gramlich M, Drenckhahn JD, Heuser A, Berger F, Jenni R, Thierfelder L: Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation 2008; 117: 2893-2901.
8. Perrot A, Schmidt-Traub H, Hoffmann B, Prager M, Bit-Avragim N, Rudenko RI, Usupbaeva DA, Kabaeva Z, Imanov B, Mirrakhimov MM, Dietz R, Wycisk A, Tendera M, Gessner R, Osterziel KJ: Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy. J Mol Med 2005; 83: 468-477.
9. Arad M, Penas-Lado M, Monserrat L, Maron BJ, Sherrid M, Ho CY, Barr S, Karim A, Olson TM, Kamisago M, Seidman JG, Seidman CE: Gene mutations in apical hypertrophic cardiomyopathy. Circulation 2005; 112: 2805-2811.
10. Engberding R, Yelbuz TM, Breithardt G: Isolated noncompaction of the left ventricular myocardium - a review of the literature two decades after the initial case description. Clin Res Cardiol 2007; 96: 481-488.
11. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB: Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807-1816.
12. Anderson RH: Ventricular non-compaction - a frequently ignored finding? Eur Heart J 2008; 29: 10-11.
13. Frazier A, Judge DP, Schulman SP, Johnson N, Holmes KW, Murphy AM: Familial hypertrophic cardiomyopathy associated with cardiac beta-myosin heavy chain and troponin I mutations. Pediatr Cardiol 2008; 29: 846-850.
14. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE: Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4,111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 1995; 92: 785-789.
15. Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH: Developmental patterning of the myocardium. Anat Rec 2000; 258: 319-337.
16. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R: Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990; 82: 507-513.
17. Rampazzo A, Nava A, Danieli GA, Buja G, Daliento L, Fasoli G, Scognamiglio R, Corrado D, Thiene G: The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q 24. Hum Mol Genet 1994; 3: 959-962.
18. Huhta JC, Chamizo W, McCormack J, Barness EG, Pomerance HH: Fifteen-year-old boy with stress-induced arrhythmia and sudden death. Am J Med Genet 2002; 111: 335-343.
19. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, Camerini F: Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J 1994; 71: 215-218.
20. Watkins H, Ashrafian H, McKenna WJ: The genetics of hypertrophic cardiomyopathy: Teare redux. Heart 2008; 94: 1264-1268.
21. Daehmlow S, Erdmann J, Knueppel T, Gille C, Froemmel C, Hummel M, Hetzer R, Regitz-Zagrosek V: Novel mutations in sarcomeric protein genes in dilated cardiomyopathy. Biochem Biophys Res Commun 2002; 298: 116-120.
22. Morimoto S: Sarcomeric proteins and inherited cardiomyopathies. Cardiovasc Res 2008; 77: 659-666.
23. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG: A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 1990; 62: 999-1006.
24. Carniel E, Taylor MR, Sinagra G, Di LA, Ku L, Fain PR, Boucek MM, Cavanaugh J, Miocic S, Slavov D, Graw SL, Feiger J, Zhu XZ, Dao D, Ferguson DA, Bristow MR, Mestroni L: Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy. Circulation 2005; 112: 54-59.
25. Epstein ND: The molecular biology and pathophysiology of hypertrophic cardiomyopathy due to mutations in the beta myosin heavy chains and the essential and regulatory light chains. Adv Exp Med Biol 1998; 453: 105-114.
26. Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND: Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet 1996; 13: 63-69.
27. Flavigny J, Richard P, Isnard R, Carrier L, Charron P, Bonne G, Forissier JF, Desnos M, Dubourg O, Komajda M, Schwartz K, Hainque B: Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy. J Mol Med 1998; 76: 208-214.
28. 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.
29. Mogensen J, Klausen IC, Pedersen AK, Egeblad H, Bross P, Kruse TA, Gregersen N, Hansen PS, Baandrup U, Borglum AD: Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J Clin Invest 1999; 103:R39-R43.
30. Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE: Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 1994; 77: 701-712.
31. Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T: Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet 1997; 16: 379-382.
32. Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG: Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med 1995; 332: 1058-1064.
33. Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M, Holmes KC, Milligan RA: Structure of the actin-myosin complex and its implications for muscle contraction. Science 1993; 261: 58-65.
34. Phillips GN Jr, Fillers JP, Cohen C: Tropomyosin crystal structure and muscle regulation. J Mol Biol 1986; 192: 111-131.
35. Weber A, Murray JM: Molecular control mechanisms in muscle contraction. Physiol Rev 1973; 53: 612-673.
36. Blankenfeldt W, Thoma NH, Wray JS, Gautel M, Schlichting I: Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment. Proc Natl Acad Sci USA 2006; 103: 17713-17717.
37. Seidman JG, Seidman C: The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 2001; 104: 557-567.
38. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M: Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003; 107: 2227-2232.
39. Wang S, Zou Y, Fu C, Xu X, Wang J, Song L, Wang H, Chen J, Wang J, Huan T, Hui R: Worse prognosis with gene mutations of beta-myosin heavy chain than myosin-binding protein C in Chinese patients with hypertrophic cardiomyopathy. Clin Cardiol 2008; 31: 114-118.
40. Woo A, Rakowski H, Liew JC, Zhao MS, Liew CC, Parker TG, Zeller M, Wigle ED, Sole MJ: Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart 2003; 89: 1179-1185.
41. Miroshnichenko NS, Balanuk IV, Nozdrenko DN: Packing of myosin molecules in muscle thick filaments. Cell Biol Int 2000; 24: 327-333.
42. Anan R, Greve G, Thierfelder L, Watkins H, McKenna WJ, Solomon S, Vecchio C, Shono H, Nakao S, Tanaka H: Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest 1994; 93: 280-285.
43. Roopnarine O, Leinwand LA: Functional analysis of myosin mutations that cause familial hypertrophic cardiomyopathy. Biophys J 1998; 75: 3023-3030.
44. Ng PC, Henikoff S: Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet 2006; 7: 61-80.
45. The Criteria Committee of the New York Heart Association: Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels, ed 9. Boston, Little, Brown & Co., 1994.
46. Kyte J, Doolittle RF: A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982; 157: 105-132.
47. Jenni R, Oechslin E, Schneider J, Attenhofer JC, Kaufmann PA: Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 2001; 86: 666-671.
48. Bax JJ, Lamb HJ, Poldermans D, Schalij MJ, de Roos A, van der Wall EE: Non-compaction cardiomyopathy-echocardiographic diagnosis. Eur J Echocardiogr 2002; 3: 301-302.
49. Nakajima-Taniguchi C, Matsui H, Eguchi N, Nagata S, Kishimoto T, Yamauchi-Takihara K: A novel deletion mutation in the beta-myosin heavy chain gene found in Japanese patients with hypertrophic cardiomyopathy. J Mol Cell Cardiol 1995; 27: 2607-2612. (Pubitemid 26003189)
50. Tesson F, Richard P, Charron P, Mathieu B, Cruaud C, Carrier L, Dubourg O, Lautie N, Desnos M, Millaire A, Isnard R, Hagege AA, Bouhour JB, Bennaceur M, Hainque B, Guicheney P, Schwartz K, Komajda M: Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy. Hum Mutat 1998; 12: 385-392.
51. Waldmuller S, Sakthivel S, Saadi AV, Selignow C, Rakesh PG, Golubenko M, Joseph PK, Padmakumar R, Richard P, Schwartz K, Tharakan JM, Rajamanickam C, Vosberg HP: Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy. J Mol Cell Cardiol 2003; 35: 623-636.
52. Moric E, Mazurek U, Polonska J, Domal-Kwiatkowska D, Smolik S, Kozakiewicz K, Tendera M, Wilczok T: Three novel mutations in exon 21 encoding beta-cardiac myosin heavy chain. J Appl Genet 2003; 44: 103-109.
53. Lowey S: Functional consequences of mutations in the myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy. Trends Cardiovasc Med 2002; 12: 348-354.
54. Geeves MA, Fedorov R, Manstein DJ: Molecular mechanism of actomyosin-based motility. Cell Mol Life Sci 2005; 62: 1462-1477.
55. Hernandez OM, Jones M, Guzman G, Szczesna-Cordary D: Myosin essential light chain in health and disease. Am J Physiol Heart Circ Physiol 2007; 292:H1643-H1654.
56. Gundapaneni D, Xu J, Root DD: High flexibility of the actomyosin crossbridge resides in skeletal muscle myosin subfragment-2 as demonstrated by a new single molecule assay. J Struct Biol 2005; 149: 117-126.
57. Watkins H: Hypertrophic cardiomyopathy: from molecular and genetic mechanisms to clinical management. Eur Heart J Suppl 2001; 3:L43-L50.
58. Opie LH, Solaro RJ: Myocardial contraction and relaxation; in Opie LH (ed): Heart Physiology: From Cell to Circulation, ed 4. London, Lippincott, Williams and Wilkins, 2004, pp 221-246.
59. Buvoli M, Hamady M, Leinwand LA, Knight R: Bioinformatics assessment of beta-myosin mutations reveals myosin's high sensitivity to mutations. Trends Cardiovasc Med 2008; 18: 141-149.
60. Blair E, Redwood C, de Jesus OM, Moolman-Smook JC, Brink P, Corfield VA, Ostman-Smith I, Watkins H: Mutations of the light meromyosin domain of the beta-myosin heavy chain rod in hypertrophic cardiomyopathy. Circ Res 2002; 90: 263-269.
61. Rayment I, Holden HM, Sellers JR, Fananapazir L, Epstein ND: Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci USA 1995; 92: 3864-3868.
62. Meurs KM, Hendrix KP, Norgard MM: Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy. Am J Vet Res 2008; 69: 1050-1053.
63. Meurs KM, Norgard MM, Kuan M, Haggstrom J, Kittleson M: Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2009; 23: 840-843.
64. Epstein ND, Cohn GM, Cyran F, Fananapazir L: Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu-Val mutation and a 403Arg-Gln mutation. Circulation 1992; 86: 345-352.
65. Volkmann N, Lui H, Hazelwood L, Trybus KM, Lowey S, Hanein D: The R403Q myosin mutation implicated in familial hypertrophic cardiomyopathy causes disorder at the actomyosin interface. PLoS ONE 2007; 2: e1123.
66. Tyska MJ, Hayes E, Giewat M, Seidman CE, Seidman JG, Warshaw DM: Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy. Circ Res 2000; 86: 737-744.
67. Debold EP, Schmitt JP, Patlak JB, Beck SE, Moore JR, Seidman JG, Seidman C, Warshaw DM: Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse alphacardiac myosin in the laser trap assay. Am J Physiol Heart Circ Physiol 2007; 293:H284-H291.
68. Ackerman MJ, VanDriest SL, Ommen SR, Will ML, Nishimura RA, Tajik AJ, Gersh BJ: Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy: a comprehensive outpatient perspective. J Am Coll Cardiol 2002; 39: 2042-2048.
69. Palmer BM, Wang Y, Teekakirikul P, Hinson JT, Fatkin D, Strouse S, Vanburen P, Seidman CE, Seidman JG, Maughan DW: Myofilament mechanical performance is enhanced by R403Q myosin in mouse myocardium independent of sex. Am J Physiol Heart Circ Physiol 2008; 294:H1939-H1947.
70. Olsson MC, Palmer BM, Stauffer BL, Leinwand LA, Moore RL: Morphological and functional alterations in ventricular myocytes from male transgenic mice with hypertrophic cardiomyopathy. Circ Res 2004; 94: 201-207.
71. Gao WD, Perez NG, Seidman CE, Seidman JG, Marban E: Altered cardiac excitationcontraction coupling in mutant mice with familial hypertrophic cardiomyopathy. J Clin Invest 1999; 103: 661-666.
72. Nagueh SF, Chen S, Patel R, Tsybouleva N, Lutucuta S, Kopelen HA, Zoghbi WA, Quinones MA, Roberts R, Marian AJ: Evolution of expression of cardiac phenotypes over a 4-year period in the beta-myosin heavy chain-Q403 transgenic rabbit model of human hypertrophic cardiomyopathy. J Mol Cell Cardiol 2004; 36: 663-673.
73. Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW, Calabrese F, Maron BJ, Thiene G: Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease. Circulation 2004; 109: 1180-1185.
74. Oyama MA, Reiken S, Lehnart SE, Chittur SV, Meurs KM, Stern J, Marks AR: Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency. J Vet Cardiol 2008; 10: 1-10.
75. Keller DI, Coirault C, Rau T, Cheav T, Weyand M, Amann K, Lecarpentier Y, Richard P, Eschenhagen T, Carrier L: Human homozygous R403W mutant cardiac myosin presents disproportionate enhancement of mechanical and enzymatic properties. J Mol Cell Cardiol 2004; 36: 355-362.
76. Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG: Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med 1992; 326: 1108-1114.
77. Posen BM, Moolman JC, Corfield VA, Brink PA: Clinical and prognostic evaluation of familial hypertrophic cardiomyopathy in two South African families with different cardiac beta myosin heavy chain gene mutations. Br Heart J 1995; 74: 40-46.
78. Marian AJ, Mares A Jr, Kelly DP, Yu QT, Abchee AB, Hill R, Roberts R: Sudden cardiac death in hypertrophic cardiomyopathy. Variability in phenotypic expression of betamyosin heavy chain mutations. Eur Heart J 1995; 16: 368-376.
79. Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG: Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function. Proc Natl Acad Sci USA 2006; 103: 14525-14530.
80. Crilley JG, Boehm EA, Blair E, Rajagopalan B, Blamire AM, Styles P, McKenna WJ, Ostman-Smith I, Clarke K, Watkins H: Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol 2003; 41: 1776-1782.
81. Consevage MW, Salada GC, Baylen BG, Ladda RL, Rogan PK: A new missense mutation, Arg719Gln, in the beta-cardiac heavy chain myosin gene of patients with familial hypertrophic cardiomyopathy. Hum Mol Genet 1994; 3: 1025-1026.
82. Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, Ackerman MJ: Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 44: 1903-1910.
83. Geisterfer-Lowrance AA, Christe M, Conner DA, Ingwall JS, Schoen FJ, Seidman CE, Seidman JG: A mouse model of familial hypertrophic cardiomyopathy. Science 1996; 272: 731-734.
84. Fatkin D, Christe ME, Aristizabal O, Mc-Connell BK, Srinivasan S, Schoen FJ, Seidman CE, Turnbull DH, Seidman JG: Neonatal cardiomyopathy in mice homozygous for the Arg403Gln mutation in the alpha cardiac myosin heavy chain gene. J Clin Invest 1999; 103: 147-153.
85. McConnell BK, Jones KA, Fatkin D, Arroyo LH, Lee RT, Aristizabal O, Turnbull DH, Georgakopoulos D, Kass D, Bond M, Niimura H, Schoen FJ, Conner D, Fischman DA, Seidman CE, Seidman JG: Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice. J Clin Invest 1999; 104: 1771.