Molecular and Cellular Biochemistry

, Volume 263, Issue 1, pp 115–129 | Cite as

Role of troponin T in disease

  • Aldrin V. Gomes
  • Junor A. Barnes
  • Keita Harada
  • James D. Potter


Several striated muscle myopathies have been directly linked to mutations in contractile and associated proteins. Troponin T (TnT) is one of the three subunits that form troponin (Tn) which together with tropomyosin is responsible for the regulation of striated muscle contraction. All three subunits of cardiac Tn as well as tropomyosin have been associated with hypertrophic cardiomyopathy (HCM). However, TnT accounts for most of the mutations that cause HCM in these regulatory proteins. To date 30 mutations have been identified in the cardiac TnT (CTnT) gene that results in familial HCM (FHC). The CTnT gene has also been associated with familial dilated cardiomyopathy (DCM). CTnT deficiency is lethal due to impaired cardiac development. A recessive nonsense mutation in the gene encoding slow skeletal TnT has been associated with an unusual, severe form of nemaline myopathy among the Old Order Amish. How each mutation leads to the diverse clinical symptoms associated with FHC, DCM or nemaline myopathy is unclear. However, the use of animal model systems, in particular transgenic mice, has significantly increased our knowledge of normal and myopathic muscle physiology. In this review, we focus on the role of TnT in muscle physiology and disease. (Mol Cell Biochem 263: 115–129, 2004)

troponin T calcium muscle contraction nemaline myopathy dilated cardiomyopathy hypertrophic cardiomyopathy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    McKenna WJ, Camm AJ: Sudden death in hypertrophic cardiomyopa-thy. Assessment of patients at high risk. Circulation 80: 148 9–1492, 1989Google Scholar
  2. 2.
    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 4111 subjects in the CAR-DIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 92: 785–789, 1995Google Scholar
  3. 3.
    Roberts R: Molecular genetics. Therapy or terror? Circulation 89: 499–502, 1994Google Scholar
  4. 4.
    Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG: A molecular basis for familial hyper-trophic cardiomyopathy: A beta cardiac myosin heavy chain gene mis-sense mutation. Cell 62: 999–1006, 1990Google Scholar
  5. 5.
    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 13: 63–69, 1996Google Scholar
  6. 6.
    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 77: 701–712, 1994Google Scholar
  7. 7.
    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 hy-pertrophic cardiomyopathy. Nat Genet 11: 434–437, 1995Google Scholar
  8. 8.
    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, Kamajda M, Schwartz K: Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nat Genet 11: 438–440, 1995Google Scholar
  9. 9.
    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 16:379–382, 1997Google Scholar
  10. 10.
    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 103: R39–R43, 1999Google Scholar
  11. 11.
    Satoh M, Takahashi M, Sakamoto T, Hiroe M, Marumo F, Kimura A: Structural analysis of the titin gene in hypertrophic cardiomyopathy: Identification of a novel disease gene. Biochem Biophys Res Commun 262: 411–417, 1999Google Scholar
  12. 12.
    Hoffmann B, Schmidt-Traub H, Perrot A, Osterziel KJ, Gessner R: First mutation in cardiac troponin C, L29Q, in a patient with hyper-trophic cardiomyopathy. Hum Mutat 17: 524, 2001Google Scholar
  13. 13.
    Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA: Frequency and phenotypes of familial dilated cardiomyopathy. J Am Coll Cardiol 31: 186–194, 1998Google Scholar
  14. 14.
    Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE: Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med 343: 1688–1696, 2000Google Scholar
  15. 15.
    Li D, Czernuszewicz GZ, Gonzalez O, Tapscott T, Karibe A, Durand JB, Brugada R, Hill R, Gregoritch JM, Anderson JL, Quinones M, Bachinski LL, Roberts R: Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy. Circulation 104: 2188–2193, 2001Google Scholar
  16. 16.
    Ilkovski B, Cooper ST, Nowak K, Ryan MM, Yang N, Schnell C, Durling HJ, Roddick LG, Wilkinson I, Kornberg AJ, Collins KJ, Wallace G, Gunning P, Hardeman EC, Laing NG, North KN: Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene. Am J Hum Genet 68: 1333–1343, 2001Google Scholar
  17. 17.
    Durling HJ, Reilich P, Muller-Hocker J, Mendel B, Pongratz D, Wallgren-Pettersson C, Gunning P, Lochmuller H, Laing NG: De novo missense mutation in a constitutively expressed exon of the slowalpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy. Neuromuscul Disord 12:947–951, 2002Google Scholar
  18. 18.
    Donner K, Ollikainen M, Ridanpaa M, Christen HJ, Goebel HH, de Visser M, Pelin K, Wallgren-Pettersson C: Mutations in the beta-tropomyosin (TPM2) gene—A rare cause of nemaline myopathy. Neuromuscul Disord 12: 151–158, 2002Google Scholar
  19. 19.
    Wallgren-Pettersson C, Donner K, Sewry C, Bijlsma E, Lammens M, Bushby K, Giovannucci Uzielli ML, Lapi E, Odent S, Akcoren Z, Topaloglu H, Pelin K: Mutations in the nebulin gene can cause se-vere congenital nemaline myopathy. Neuromuscul Disord 12: 674–679, 2002Google Scholar
  20. 20.
    Johnston JJ, Kelley RI, Crawford TO, Morton DH, Agarwala R, Koch T, Schaffer AA, Francomano CA, Biesecker LG: A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet 67: 814–821, 2000Google Scholar
  21. 21.
    Sanoudou D, Beggs AH: Clinical and genetic heterogeneity in nema-line myopathy—A disease of skeletal muscle thin filaments. Trends Mol Med 7: 362–368, 2001Google Scholar
  22. 22.
    Ebashi S: Regulation of the myosin-actin interaction by the Ca 2 +-troponin–tropomyosin system. J Biochem (Tokyo) 79: 48P–49P, 1976Google Scholar
  23. 23.
    Zot AS, Potter JD: Structural aspects of troponin-tropomyosin regula-tion of skeletal muscle contraction. Annu Rev Biophys Biophys Chem 16: 535–559, 1987Google Scholar
  24. 24.
    White SP, Cohen C, Phillips GN Jr.: Structure of co-crystals of tropomyosin and troponin. Nature 325: 826–828, 1987Google Scholar
  25. 25.
    Stefancsik R, Jha PK, Sarkar S: Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I bind-ing: Potential role for coiled coil interaction. Proc Natl Acad Sci USA 95: 957–962, 1998Google Scholar
  26. 26.
    Takeda S, Yamashita A, Maeda K, Maeda Y: Structure of the core domain of human cardiac troponin in the Ca 2 + saturated form. Nature 424: 35–41, 2003Google Scholar
  27. 27.
    Potter JD, Sheng Z, Pan BS, Zhao J: A direct regulatory role for tro-ponin T and a dual role for troponin C in the Ca 2 + regulation of muscle contraction. J Biol Chem 270: 2557–2562, 1995Google Scholar
  28. 28.
    Fraser ID, Marston SB: In vitro motility analysis of actin-tropomyosin regulation by troponin and calcium. The thin filament is switched as a single cooperative unit. J Biol Chem 270: 7836–7841, 1995Google Scholar
  29. 29.
    Sehnert AJ, Huq A, Weinstein BM, Walker C, Fishman M, Stainier DY: Cardiac troponin T is essential in sarcomere assembly and cardiac contractility. Nat Genet 31: 106–110, 2002Google Scholar
  30. 30.
    Perry SV: Troponin T: genetics, properties and function. J Muscle Res Cell Motil 19: 575–602, 1998Google Scholar
  31. 31.
    Farza H, Townsend PJ, Carrier L, Barton PJ, Mesnard L, Bahrend E, Forissier JF, Fiszman M, Yacoub MH, Schwartz K: Genomic organi-sation, alternative splicing and polymorphisms of the human cardiac troponin T gene. J Mol Cell Cardiol 30: 1247–1253, 1998Google Scholar
  32. 32.
    Townsend PJ, Barton PJ, Yacoub MH, Farza H: Molecular cloning of human cardiac troponin T isoforms: Expression in developing and failing heart. J Mol Cell Cardiol 27: 2223–2236, 1995Google Scholar
  33. 33.
    Antin PB, Zhang W, Bales MA, Garriock RJ, Yatskievych TA: Pre-cocious expression of cardiac troponin T in early chick embryos is independent of bone morphogenetic protein signaling. Dev Dyn 225: 376, 2002Google Scholar
  34. 34.
    Gomes AV, Guzman G, Zhao J, Potter JD: Cardiac troponin T isoforms affect the Ca 2 + sensitivity and inhibition of force development. Insights into the role of troponin T isoforms in the heart. J Biol Chem 277: 35341–35349, 2002Google Scholar
  35. 35.
    Schachat FH, Diamond MS, Brandt PW: Effect of different troponin T-tropomyosin combinations on thin filament activation. J Mol Biol 198: 551–554, 1987Google Scholar
  36. 36.
    Tobacman LS, Lee R: Isolation and functional comparison of bovine cardiac troponin T isoforms. J Biol Chem 262: 4059–4064, 1987Google Scholar
  37. 37.
    Knollmann BC, Potter JD: Altered regulation of cardiac muscle con-traction by troponin T mutations that cause familial hypertrophic car-diomyopathy. Trends Cardiovasc Med 11: 206–212, 2001Google Scholar
  38. 38.
    Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG, Seidman CE: Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med 332: 1058–1064, 1995Google Scholar
  39. 39.
    Anan R, Shono H, Kisanuki A, Arima S, Nakao S, Tanaka H: Patients with familial hypertrophic cardiomyopathy caused by a Phe110Ile mis-sense mutation in the cardiac troponin T gene have variable cardiac morphologies and a favorable prognosis. Circulation 98: 391–397, 1998Google Scholar
  40. 40.
    Forissier JF, Carrier L, Farza H, Bonne G, Bercovici J, Richard P, Hainque B, Townsend PJ, Yacoub MH, Faure S, Dubourg O, Millaire A, Hagege AA, Desnos M, Komajda M, Schwartz K: Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in familial hypertrophic cardiomyopathy. Circulation 94: 3069–3073, 1996Google Scholar
  41. 41.
    Lin T, Ichihara S, Yamada Y, Nagasaka T, Ishihara H, Nakashima N, Yokota M: Phenotypic variation of familial hypertrophic cardiomy-opathy caused by the Phe(110) → Ile mutation in cardiac troponin T. Cardiology 93: 155–162, 2000Google Scholar
  42. 42.
    Ho CY, Lever HM, DeSanctis R, Farver CF, Seidman JG, Seidman CE: Homozygous mutation in cardiac troponin T: Implications for hypertrophic cardiomyopathy. Circulation 102: 1950–1955, 2000Google Scholar
  43. 43.
    Nakajima-Taniguchi C, Matsui H, Fujio Y, Nagata S, Kishimoto T, Yamauchi-Takihara K: Novel missense mutation in cardiac troponin T gene found in Japanese patient with hypertrophic cardiomyopathy. J Mol Cell Cardiol 29: 839–843, 1997Google Scholar
  44. 44.
    Varnava A, Baboonian C, Davison F, de Cruz L, Elliott PM, Davies MJ, McKenna WJ: A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy. Heart 82: 621–624, 1999Google Scholar
  45. 45.
    Szczesna D, Zhang R, Zhao J, Jones M, Guzman G, Potter JD: Altered regulation of cardiac muscle contraction by troponin T mutations that cause familial hypertrophic cardiomyopathy. J Biol Chem 275: 624–630, 2000Google Scholar
  46. 46.
    Tobacman LS, Lin D, Butters C, Landis C, Back N, Pavlov D, Homsher E: Functional consequences of troponin T mutations found in hypertrophic cardiomyopathy. J Biol Chem 274: 28363–28370, 1999Google Scholar
  47. 47.
    Nakaura H, Yanaga F, Ohtsuki I, Morimoto S: Effects of missense mutations Phe110Ile and Glu244Asp in human cardiac troponin T on force generation in skinned cardiac muscle fibers. J Biochem (Tokyo) 126: 457–460, 1999Google Scholar
  48. 48.
    Takahashi-Yanaga F, Ohtsuki I, Morimoto S: Effects of troponin T mu-tations in familial hypertrophic cardiomyopathy on regulatory func-tions of other troponin subunits. J Biochem (Tokyo) 130: 127–131, 2001Google Scholar
  49. 49.
    Harada K, Takahashi-Yanaga F, Minakami R, Morimoto S, Ohtsuki I: Functional consequences of the deletion mutation deltaGlu160 in human cardiac troponin T. J Biochem (Tokyo) 127: 263–268, 2000Google Scholar
  50. 50.
    Mukherjea P, Tong L, Seidman JG, Seidman CE, Hitchcock-DeGregori SE: Altered regulatory function of two familial hypertrophic cardiomy-opathy troponin T mutants. Biochemistry 38: 13296–13301, 1999Google Scholar
  51. 51.
    Nakaura H, Morimoto S, Yanaga F, Nakata M, Nishi H, Imaizumi T, Ohtsuki I: Functional changes in troponin T by a splice donor site mutation that causes hypertrophic cardiomyopathy. Am J Physiol 277: C225–C232, 1999Google Scholar
  52. 52.
    Redwood C, Lohmann K, Bing W, Esposito GM, Elliott K, Abdul-razzak H, Knott A, Purcell I, Marston S, Watkins H: Investigation of a truncated cardiac troponin T that causes familial hypertrophic cardiomyopathy: Ca 2 + regulatory properties of reconstituted thin fila-ments depend on the ratio of mutant to wild-type protein. Circ Res 86: 1146–1152, 2000Google Scholar
  53. 53.
    Schonberger J, Seidman CE: Many roads lead to a broken heart: The genetics of dilated cardiomyopathy. Am J Hum Genet 69: 249–260, 2001Google Scholar
  54. 54.
    Hanson EL, Jakobs PM, Keegan H, Coates K, Bousman S, Dienel NH, Litt M, Hershberger RE: Cardiac troponin T lysine 210 deletion in a family with dilated cardiomyopathy. J Card Fail 8: 28–32, 2002Google Scholar
  55. 55.
    Moolman JC, Corfield VA, Posen B, Ngumbela K, Seidman C, Brink PA, Watkins H: Sudden death due to troponin T mutations. J Am Coll Cardiol 29: 549–555, 1997Google Scholar
  56. 56.
    Fujino N, Shimizu M, Ino H, Okeie K, Yamaguchi M, Yasuda T, Kokado H, Mabuchi H: Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy. Clin Cardiol 24: 397–402, 2001Google Scholar
  57. 57.
    Fujino N, Shimizu M, Ino H, Yamaguchi M, Yasuda T, Nagata M, Konno T, Mabuchi H: A novel mutation Lys273Glu in the cardiac troponin T gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy. Am J Cardiol 89: 29–33, 2002Google Scholar
  58. 58.
    Robinson P, Mirza M, Knott A, Abdulrazzak H, Willott R, Marston S, Watkins H, Redwood C: Alterations in thin filament regulation induced by a human cardiac troponin T mutant that causes dilated cardiomy-opathy are distinct from those induced by troponin T mutants that cause hypertrophic cardiomyopathy. J Biol Chem 277: 40710–40716, 2002Google Scholar
  59. 59.
    Morimoto S, Lu QW, Harada K, Takahashi-Yanaga F, Minakami R, Ohta M, Sasaguri T, Ohtsuki I: Ca(2 +)-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy. Proc Natl Acad Sci USA 99: 913–918, 2002Google Scholar
  60. 60.
    Marian AJ, Roberts R: On Koch's postulates, causality and genetics of cardiomyopathies. J Mol Cell Cardiol 34: 971–974, 2002Google Scholar
  61. 61.
    Oberst L, Zhao G, Park JT, Brugada R, Michael LH, Entman ML, Roberts R, Marian AJ: Dominant-negative effect of a mutant cardiac troponin T on cardiac structure and function in transgenic mice. J Clin Invest 102: 1498–1505, 1998Google Scholar
  62. 62.
    Lim DS, Oberst L, McCluggage M, Youker K, Lacy J, DeMayo F, Entman ML, Roberts R, Michael LH, Marian AJ: Decreased left ven-tricular ejection fraction in transgenic mice expressing mutant cardiac troponin T-Q(92), responsible for human hypertrophic cardiomyopa-thy. J Mol Cell Cardiol 32: 365–374, 2000Google Scholar
  63. 63.
    Tardiff JC, Hewett TE, Palmer BM, Olsson C, Factor SM, Moore RL, Robbins J, Leinwand LA: Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic car-diomyopathy. J Clin Invest 104: 469–481, 1999Google Scholar
  64. 64.
    Tardiff JC, Factor SM, Tompkins BD, Hewett TE, Palmer BM, Moore RL, Schwartz S, Robbins J, Leinwand LA: Atruncated cardiac troponin T molecule in transgenic mice suggests multiple cellular mechanisms for familial hypertrophic cardiomyopathy. J Clin Invest 101: 2800–2811, 1998Google Scholar
  65. 65.
    Frey N, Franz WM, Gloeckner K, Degenhardt M, Muller M, Muller O, Merz H, Katus HA: Transgenic rat hearts expressing a human car-diac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias. Cardiovasc Res 47: 254–264, 2000Google Scholar
  66. 66.
    Knollmann BC, Blatt SA, Horton K, de Freitas F, Miller T, Bell M, Housmans PR, Weissman NJ, Morad M, Potter JD: Inotropic stim-ulation induces cardiac dysfunction in transgenic mice expressing a troponin T (I79N) mutation linked to familial hypertrophic cardiomy-opathy. J Biol Chem 276: 10039–10048, 2001Google Scholar
  67. 67.
    Miller T, Szczesna D, Housmans PR, Zhao J, de Freitas F, Gomes AV, Culbreath L, McCue J, Wang Y, Xu Y, Kerrick WG, Potter JD: Abnormal contractile function in transgenic mice expressing a familial hypertrophic cardiomyopathy-linked troponin T (I79N) mutation. J Biol Chem 276: 3743–3755, 2001Google Scholar
  68. 68.
    Gomes AV, Miller T, Jaquez O, Ampie L, Potter JD: Impaired regu-latory properties of a truncated slow skeletal troponin T that causes nemaline myopathy. Biophys J 84: 319A, 2003Google Scholar
  69. 69.
    Yuasa K, Michibata H, Omori K, Yanaka N: A novel interaction of cGMP-dependent protein kinase I with troponin T. J Biol Chem 274: 37429–37434, 1999Google Scholar
  70. 70.
    Jaquet K, Fukunaga K, Miyamoto E, Meyer HE: A site phosphory-lated in bovine cardiac troponin T by cardiac CaM kinase II. Biochim Biophys Acta 1248: 193–195, 1995Google Scholar
  71. 71.
    Noland TA Jr., Kuo JF: Protein kinase C phosphorylation of cardiac troponin I and troponin T inhibits Ca(2 +)-stimulated MgATPase activ-ity in reconstituted actomyosin and isolated myofibrils, and decreases actin-myosin interactions. J Mol Cell Cardiol 25: 53–65, 1993Google Scholar
  72. 72.
    Morimoto S, Yanaga F, Minakami R, Ohtsuki I: Ca 2 +-sensitizing ef-fects of the mutations at Ile-79 and Arg-92 of troponin Tin hypertrophic cardiomyopathy. Am J Physiol 275: C200–C207, 1998Google Scholar
  73. 73.
    Biesiadecki BJ, Elder BD, Yu ZB, Jin JP: Cardiac troponin T variants produced by aberrant splicing of multiple exons in animals with high instances of dilated cardiomyopathy. J Biol Chem 107, 2002Google Scholar
  74. 74.
    Palm T, Graboski S, Hitchcock-DeGregori SE, Greenfield NJ: Disease-causing mutations in cardiac troponin T: Identification of a critical tropomyosin-binding region. Biophys J 81: 2827–2837, 2001Google Scholar
  75. 75.
    Sarko J, Pollack CV Jr.: Cardiac troponins. J Emerg Med 23: 57–65, 2002Google Scholar
  76. 76.
    Mair J: Cardiac troponin I and troponin T: Are enzymes still relevant as cardiac markers? Clin Chim Acta 257: 99–115, 1997Google Scholar
  77. 77.
    Wu AH, Feng YJ, Moore R, Apple FS, McPherson PH, Buechler KF, Bodor G: Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Sub-committee on cTnI Standardization. Clin Chem 44: 1198–1208, 1998Google Scholar
  78. 78.
    Panteghini M, Gerhardt W, Apple FS, Dati F, Ravkilde J, Wu AH: Quality specifications for cardiac troponin assays. Clin Chem Lab Med 39: 175–179, 2001Google Scholar
  79. 79.
    Katus HA, Remppis A, Scheffold T, Diederich KW, Kuebler W: Intra-cellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction. Am J Cardiol 67: 1360–1367, 1991Google Scholar
  80. 80.
    Voss EM, Sharkey SW, Gernert AE, Murakami MM, Johnston RB, Hsieh CC, Apple FS: Human and canine cardiac troponin T and crea-tine kinase-MB distribution in normal and diseased myocardium. In-farct sizing using serum profiles. Arch Pathol Lab Med 119: 799–806, 1995Google Scholar
  81. 81.
    Ricchiuti V, Zhang J, Apple FS: Cardiac troponin I and T alterations in hearts with severe left ventricular remodeling. Clin Chem 43: 990–995, 1997Google Scholar
  82. 82.
    Varnava AM, Elliott PM, Baboonian C, Davison F, Davies MJ, McKenna WJ: Hypertrophic cardiomyopathy: Histopathological fea-tures of sudden death in cardiac troponin T disease. Circulation 104:1380–1384, 2001Google Scholar
  83. 83.
    Marian AJ, Roberts R: The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol 33:655–670, 2001Google Scholar
  84. 84.
    D'Cruz LG, Baboonian C, Phillimore HE, Taylor R, Elliott PM, Varnava A, Davison F, McKenna WJ, Carter ND: Cytosine methylation confers instability on the cardiac troponin T gene in hypertrophic car-diomyopathy. J Med Genet 37: E18, 2000Google Scholar
  85. 85.
    Ackerman MJ, VanDriest SL, Ommen SR, Will ML, Nishimura RA, Tajik AJ, Gersh BJ: Prevalence and age-dependence of malignant mu-tations in the beta-myosin heavy chain and troponin T genes in hy-pertrophic cardiomyopathy: A comprehensive outpatient perspective. J AmColl Cardiol 39: 2042–2048, 2002Google Scholar
  86. 86.
    Yanaga F, Morimoto S, Ohtsuki I: Ca 2 + sensitization and potentiation of the maximum level of myofibrillar ATPase activity caused by mu-tations of troponin T found in familial hypertrophic cardiomyopathy. J Biol Chem 274: 8806–8812, 1999Google Scholar
  87. 87.
    Morimoto S, Nakaura H, Yanaga F, Ohtsuki I: Functional consequences of a carboxyl terminal missense mutation Arg278Cys in human cardiac troponin T. Biochem Biophys Res Commun 261: 79–82, 1999Google Scholar
  88. 88.
    Lin D, Bobkova A, Homsher E, Tobacman LS: Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy. J Clin Invest 97: 2842–2848, 1996Google Scholar
  89. 89.
    Harada K, Szczesna D, Hernandez O, Potter JD: Effect of human cardiac troponin T mutations linked to familial hypertrophic cardiomy-opathy (FHC) on the force-pCa relationship in skinned human muscle fibers. Biophys J 82: A391, 2002Google Scholar
  90. 90.
    Sweeney HL, Feng HS, Yang Z, Watkins H: Functional analyses of troponin T mutations that cause hypertrophic cardiomyopathy: insights into disease pathogenesis and troponin function. Proc Natl Acad Sci USA 95: 14406–14410, 1998Google Scholar
  91. 91.
    Watkins H, Seidman CE, Seidman JG, Feng HS, Sweeney HL: Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. Evidence for a dominant negative action. J Clin Invest 98: 2456–2461, 1996Google Scholar
  92. 92.
    Rust EM, Albayya FP, Metzger JM: Identification of a con-tractile deficit in adult cardiac myocytes expressing hypertrophic cardiomyopathy-associated mutant troponin T proteins. J Clin Invest 103: 1459–1467, 1999Google Scholar
  93. 93.
    Koga Y, Toshima H, Kimura A, Harada H, Koyanagi T, Nishi H, Nakata M, Imaizumi T: Clinical manifestations of hypertrophic cardiomyopa-thy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene. J Card Fail 2: S97–S103, 1996Google Scholar
  94. 95.
    Elliott PM, D'Cruz L, McKenna WJ: Late-onset hypertrophic car-diomyopathy caused by a mutation in the cardiac troponin T gene [letter]. N Engl J Med 341: 1855–1856, 1999Google Scholar
  95. 96.
    Erdmann FJ, Wischke S, Riedel K, Kallisch H, Fleck ME, Regitz-Zagrosek FV: A new mutation (Arg-278-Pro) in the cardiac troponin T gene (TNNT2) was identified in one patient with typical hypertrophic cardiomyopathy (HCM). Circulation 98: 1273, 1998Google Scholar
  96. 97.
    Watkins H, MacRae C, Thierfelder L, Chou YH, Frenneaux M, McKenna W, Seidman JG, Seidman CE: A disease locus for familial.129 hypertrophic cardiomyopathy maps to chromosome 1q3. Nat Genet 3: 333–337, 1993Google Scholar
  97. 98.
    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 107: 2227–2232, 2003Google Scholar
  98. 99.
    Van Driest SL, Ellsworth EG, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy. Circulation 108: 445–451, 2003Google Scholar
  99. 100.
    Garcia-Castro M, Reguero JR, Batalla A, Diaz-Molina B, Gonzalez P, Alvarez V, Cortina A, Cubero GI, Coto E. Hypertrophic cardiomy-opathy: Low frequency of mutations in the beta-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes among Spanish pa-tients. Clin Chem 49: 1279–1285, 2003Google Scholar
  100. 101.
    Venkatraman G, Harada K, Gomes AV, Kerrick GW, Potter JD. Different functional properties of Troponin T mutants that cause dilated cardiomyopathy. J Biol Chem 278: 41670–41676, 2003.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Aldrin V. Gomes
    • 1
  • Junor A. Barnes
    • 2
  • Keita Harada
    • 1
  • James D. Potter
    • 1
  1. 1.Department of Molecular and Cellular PharmacologyUniversity of Miami School of MedicineMiamiFlorida
  2. 2.Biochemistry UnitUniversity of the West IndiesTrinidadWest Indies

Personalised recommendations