Molecular basis of hereditary cardiomyopathy: abnormalities in calcium sensitivity, stretch response, stress response and beyond (original) (raw)

References

1. Maron, B. J., Towbin, J. A., Thiene, G., Antzelevitch, C., Corrado, D., Arnett, D. et al. 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 113, 1807–1816 (2006).
   Article PubMed Google Scholar
2. Towbin, J. A. & Bowles, N. E. The failing heart. Nature 415, 227–233 (2002).
   Article CAS PubMed Google Scholar
3. Ahmad, F., Seidman, J. G. & Seidman, C. E. The genetic basis for cardiac remodeling. Annu. Rev. Genomics Hum. Genet. 6, 185–216 (2006).
   Article CAS Google Scholar
4. Kushwaha, S. S., Fallon, J. & Fuster, V. Restrictive cardiomyopathy. N. Engl. J. Med. 336, 267–276 (1997).
   Article CAS PubMed Google Scholar
5. Seidman, J. G. & Seidman, C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 104, 557–567 (2001).
   Article CAS PubMed Google Scholar
6. Goerss, J. B., Michels, V. V., Burnett, J., Driscoll, D. J., Miller, F., Rodeheffer, R. et al. Frequency of familial dilated cardiomyopathy. Eur. Heart J. 16, O2–O4 1995)).
   Article Google Scholar
7. Mestroni, L., Rocco, C., Gregori, D., Sinagra, G., Di Lenarda, A., Miocic, S. et al. Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group. J. Am. Coll. Cardiol. 34, 181–190 (1999).
   Article CAS PubMed Google Scholar
8. Geisterfer-Lowrance, A. A. T., Kass, S., Tanigawa, G., Vosberg, H. P., McKenna, W., Seidman, C. E. et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 62, 999–1006 (1990).
   Article CAS PubMed Google Scholar
9. Nishi, H., Kimura, A., Harada, H., Adachi, K., Koga, Y., Sasazuki, T. et al. Possible gene dose effect of a mutant cardiac beta-myosin heavy chain gene on the clinical expression of familial hypertrophic cardiomyopathy. Biochem. Biophys. Res. Commun. 200, 549–556 (1994).
   Article CAS PubMed Google Scholar
10. Kimura, A., Harada, H., Park, J. E., Nishi, H., Satoh, M., Takahashi, M. et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nature Genet. 16, 379–382 (1997).
    Article CAS PubMed Google Scholar
11. Arad, M., Seidman, J. G. & Seidman, C. E. Phenotypic diversity in hypertrophic cardiomyopathy. Hum. Mol. Genet. 11, 2499–2506 (2002).
    Article CAS PubMed Google Scholar
12. Kimura, A. Molecular etiology and pathogenesis of hereditary cardiomyopathy. Circ. J. 72, A38–A48 (2008).
    Article PubMed Google Scholar
13. Watkins, H., Rosenzweig, A., Hwang, D. S., Levi, T., McKenna, W. et al. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N. Engl. J. Med. 326, 1108–1114 (1992).
    Article CAS PubMed Google Scholar
14. Harada, H., Kimura, A., Nishi, H., Sasazuki, T. & Toshima, H. A missense mutation of cardiac beta-myosin heavy chain gene linked to familial hypertrophic cardiomyopathy in affected Japanese families. Biochem. Biophys. Res. Commun. 194, 791–798 (1993).
    Article CAS PubMed Google Scholar
15. Hwang, T. H., Lee, W. H., Kimura, A., Satoh, M., Nakamura, T., Kim, M. K. et al. Early expression of a malignant phenotype of familial hypertrophic cardiomyopathy associated with a Gly716Arg myosin heavy chain mutation in a Korean family. Am. J. Cardiol. 82, 1509–1513 (1998).
    Article CAS PubMed Google Scholar
16. Nishi, H., Kimura, A., Harada, H., Koga, Y., Adachi, K., Matsuyama, K., Koyanagi, T. et al. A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy. Circulation 91, 2911–2915 (1995).
    Article CAS PubMed Google Scholar
17. Koga, Y., Toshima, H., Kimura, A., Harada, H., Koyanagi, T., Nishi, H. et al. Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene. J. Card. Fail. 2, S97–S103 (1996).
    Article CAS PubMed Google Scholar
18. Rayment, I., Holden, H. M., Sellers, J. R., Fananapazir, L. & Epstein, N. D. Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc. Natl. Acad. Sci. USA 92, 3864–3868 (1995).
    Article CAS PubMed PubMed Central Google Scholar
19. Watkins, H., McKenna, W. J., Thierfelder, L., Suk, H. J., Anan, R. et al. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N. Engl. J. Med. 332, 1058–1064 (1995).
    Article CAS PubMed Google Scholar
20. Varnava, A. M., Elliott, P. M., Baboonian, C., Davison, F., Davies, M. J. & McKenna, W. J. Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease. Circulation 104, 1380–1384 (2001).
    Article CAS PubMed Google Scholar
21. Niimura, H., Patton, K. K., McKenna, W. J., Soults, J., Maron, B. J., Seidman, J. G. et al. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 105, 446–451 (2002).
    Article CAS PubMed Google Scholar
22. Kubo, T., Kitaoka, H., Okawa, M., Matsumura, Y., Hitomi, N., Yamasaki, N. et al. Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac myosin-binding protein C gene among Japanese. J. Am. Coll. Cardiol. 46, 1737–1743 (2005).
    Article CAS PubMed Google Scholar
23. Sweeney, H. L., Straceski, A. J., Leinwand, L. A., Tikunov, B. A. & Faust, L. Heterologous expression of a cardiomyopathic myosin that is defective in its actin interaction. J. Biol. Chem. 269, 1603–1605 (1994).
    Article CAS PubMed Google Scholar
24. Thierfelder, L., Watkins, H., MacRae, C., Lamas, R., McKenna, W., Vosberg, H. P. et al. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 77, 701–712 (1994).
    Article PubMed Google Scholar
25. Yanaga, F., Morimoto, S. & Ohtsuki, I. Ca2+ sensitization and potentiation of the maximum level of myofibrillar ATPase activity caused by mutations of troponin T found in familial hypertrophic cardiomyopathy. J. Biol. Chem. 274, 8806–8812 (1999).
    Article CAS PubMed Google Scholar
26. Bottinelli, R., Coviello, D. A., Redwood, C. S., Pellegrino, M. A., Maron, B. J., Spirito, P. et al. A mutant tropomyosin that causes hypertrophic cardiomyopathy is expressed in vivo and associated with an increased calcium sensitivity. Circ. Res. 82, 106–115 (1998).
    Article CAS PubMed Google Scholar
27. Elliott, K., Watkins, H. & Redwood, C. S. Altered regulatory properties of human cardiac troponin I mutants that cause hypertrophic cardiomyopathy. J. Biol. Chem. 275, 22069–22074 (2000).
    Article CAS PubMed Google Scholar
28. Witt, C. C., Gerull, B., Davies, M. J., Centner, T., Linke, W. A. & Thierfelder, L. Hypercontractile properties of cardiac muscle fibers in a knock-in mouse model of cardiac myosin-binding protein-C. J. Biol. Chem. 276, 5353–5359 (2001).
    Article CAS PubMed Google Scholar
29. Roopnarine, O. Mechanical defects of muscle fibers with myosin light chain mutants that cause cardiomyopathy. Biophys. J. 84, 2440–2449 (2003).
    Article CAS PubMed PubMed Central Google Scholar
30. Pinto, J. R., Parvatiyar, M. S., Jones, M. A., Liang, J., Ackerman, M. J. & Potter, J. D. A functional and structural study of troponin C mutations related to hypertrophic cardiomyopathy. J. Biol. Chem. 284, 19090–19100 (2009).
    Article CAS PubMed PubMed Central Google Scholar
31. Tyska, M. J., Hayes, E., Giewat, M., Seidman, C. E., Seidman, J. G. & Warshaw, D. M. Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy. Circ. Res. 86, 737–744 (2000).
    Article CAS PubMed Google Scholar
32. 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 (1999).
    Article CAS PubMed Google Scholar
33. Hayashi, T., Arimura, T., Itoh-Satoh, M., Ueda, K., Hohda, S., Inagaki, N. et al. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. J. Am. Coll. Cardiol. 44, 2192–2201 (2004).
    Article CAS PubMed Google Scholar
34. Cazorla, O., Wu, Y., Irving, T. C. & Granzier, H. Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes. Circ. Res. 88, 1028–1035 (2001).
    Article CAS PubMed Google Scholar
35. Fujita, H., Labeit, D., Gerull, B., Labeit, S. & Granzier, H. L. Titin isoform-dependent effect of calcium on passive myocardial tension. Am. J. Physiol. Heart Circ. Physiol. 287, H2528–H2534 (2004).
    Article CAS PubMed Google Scholar
36. Fuchs, F. & Martyn, D. A. Length-dependent Ca(2+) activation in cardiac muscle: some remaining questions. J. Muscle Res. Cell Motil. 26, 199–212 (2005).
    Article CAS PubMed Google Scholar
37. Geier, C., Perrot, A., Ozcelik, C., Binner, P., Counsell, D., Hoffmann, K. et al. Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy. Circulation 107, 1390–1395 (2003).
    Article CAS PubMed Google Scholar
38. Gehmlich, K., Geier, C., Osterziel, K. J., Van der Ven, P. F. & Fürst, D. O. Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy. Cell Tissue Res. 317, 129–136 (2004).
    Article CAS PubMed Google Scholar
39. Mohapatra, B., Jimenez, S., Lin, J. H., Bowles, K. R., Coveler, K. J., Marx, J. G. et al. Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Mol. Genet. Metab. 80, 207–215 (2003).
    Article CAS PubMed Google Scholar
40. Hayashi, T., Arimura, T., Ueda, K., Shibata, H., Hohda, S., Takahashi, M. et al. Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem. Biophys. Res. Commun. 313, 178–184 (2004).
    Article CAS PubMed Google Scholar
41. Vasile, V. C., Ommen, S. R., Edwards, W. D. & Ackerman, M. J. A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. Biochem. Biophys. Res. Commun. 345, 998–1003 (2006).
    Article CAS PubMed Google Scholar
42. Wang, X., Osinska, H., Klevitsky, R., Gerdes, A. M., Nieman, M., Lorenz, J. et al. Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ. Res. 89, 84–91 (2001).
    Article CAS PubMed Google Scholar
43. Landstrom, A. P., Weisleder, N., Batalden, K. B., Bos, J. M., Tester, D. J., Ommen, S. R. et al. Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans. J. Mol. Cell Cardiol. 42, 1026–1035 (2007).
    Article CAS PubMed PubMed Central Google Scholar
44. Arimura, T., Matsumoto, Y., Okazaki, O., Hayashi, T., Takahashi, M., Inagaki, N. et al. Structural analysis of obscurin gene in hypertrophic cardiomyopathy. Biochem. Biophys. Res. Commun. 362, 281–287 (2007).
    Article CAS PubMed Google Scholar
45. Arimura, T., Bos, M. J., Sato, A., Kubo, T., Okamoto, H., Nishi, H. et al. Cardiac ankyrin repeat protein gene (ANKRD1) mutations in hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 54, 334–342 (2009).
    Article CAS PubMed Google Scholar
46. Rajasekaran, N. S., Connell, P., Christians, E. S., Yan, L. J., Taylor, R. P., Orosz, A. et al. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130, 427–439 (2007).
    Article CAS PubMed PubMed Central Google Scholar
47. Matsumoto, Y., Hayashi, T., Inagaki, N., Takahashi, M., Hiroi, S., Nakamura, T. et al. Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy. J. Muscle Res. Cell Motil. 26, 367–374 (2005).
    Article CAS PubMed Google Scholar
48. Inagaki, N., Hayashi, T., Arimura, T., Koga, Y., Takahashi, M., Shibata, H. et al. Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem. Biophys. Res. Commun. 342, 379–386 (2006).
    Article CAS PubMed Google Scholar
49. Kikuchi, T., Oka, N., Koga, A., Miyazaki, H., Ohmura, H. & Imaizumi, T. Behavior of caveolae and caveolin-3 during the development of myocyte hypertrophy. J. Cardiovasc. Pharmacol. 45, 204–210 (2005).
    Article CAS PubMed Google Scholar
50. Koga, A., Oka, N., Kikuchi, T., Miyazaki, H., Kato, S. & Imaizumi, T. Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy. Hypertension 42, 213–219 (2003).
    Article CAS PubMed Google Scholar
51. Young, P., Ehler, E. & Gautel, M. Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly. J. Cell Biol. 154, 123–136 (2001).
    Article CAS PubMed PubMed Central Google Scholar
52. Aihara, Y., Kurabayashi, M., Saito, Y., Ohyama, Y., Tanaka, T., Takeda, S. et al. Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of M-CAT element within the promoter. Hypertension 36, 48–53 (2000).
    Article CAS PubMed Google Scholar
53. Witt, S. H., Labeit, D., Granzier, H., Labeit, S. & Witt, C. C. Dimerization of the cardiac ankyrin protein CARP: implications for MARP titin-based signaling. J. Muscle Res. Cell Motil. 262, 1–8 (2006).
    Google Scholar
54. Towbin, J. A., Hejtmancik, J. F., Brink, P., Gelb, B., Zhu, X. M., Chamberlain, J. S. et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation 87, 1854–1865 (1993).
    Article CAS PubMed Google Scholar
55. Cohen, N. & Muntoni, F. Multiple pathogenetic mechanisms in X linked dilated cardiomyopathy. Heart 90, 835–841 (2004).
    Article CAS PubMed PubMed Central Google Scholar
56. Muntoni, F., Torelli, S. & Ferlini, A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2, 731–740 (2003).
    Article CAS PubMed Google Scholar
57. Finsterer, J. & Stöllberger, C. The heart in human dystrophinopathies. Cardiology 99, 1–19 (2003).
    Article PubMed Google Scholar
58. Lapidos, K. A., Kakkar, R. & McNally, E. M. The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ. Res. 94, 1023–1031 (2004).
    Article CAS PubMed Google Scholar
59. Tsubata, S., Bowles, K. R., Vatta, M., Zintz, C., Titus, J., Muhonen, L. et al. Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J. Clin. Invest. 106, 655–662 (2000).
    Article CAS PubMed PubMed Central Google Scholar
60. Knöll, R., Postel, R., Wang, J., Krätzner, R., Hennecke, G., Vacaru, A. M. et al. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation 116, 515–525 (2007).
    Article PubMed CAS Google Scholar
61. Towbin, J. A. & Bowles, N. E. Genetic abnormalities responsible for dilated cardiomyopathy. Curr. Cardiol. Rep. 2, 475–480 (2000).
    Article CAS PubMed Google Scholar
62. Olson, T. M., Michels, V. V., Thibodeau, S. N., Tai, Y. S. & Keating, M. T. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science 280, 750–752 (1998).
    Article CAS PubMed Google Scholar
63. Mogensen, J., Klausen, I. C., Pedersen, A. K., Egeblad, H., Bross, P., Kruse, T. A. et al. Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J. Clin. Invest. 103, R39–R43 (1999).
    Article CAS PubMed PubMed Central Google Scholar
64. Vang, S., Corydon, T. J., Børglum, A. D., Scott, M. D., Frydman, J., Mogensen, J. et al. Actin mutations in hypertrophic and dilated cardiomyopathy cause inefficient protein folding and perturbed filament formation. FEBS J. 272, 2037–2049 (2005).
    Article CAS PubMed Google Scholar
65. Kamisago, M., Sharma, S. D., DePalma, S. R., Solomon, S., Sharma, P., McDonough, B. et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N. Engl. J. Med. 343, 1688–1696 (2000).
    Article CAS PubMed Google Scholar
66. Morimoto, S., Lu, Q. W., Harada, K., Takahashi-Yanaga, F., Minakami, R., Ohta, M. et al. 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 (2002).
    Article CAS PubMed PubMed Central Google Scholar
67. Chang, A. N. & Potter, J. D. Sarcomeric protein mutations in dilated cardiomyopathy. Heart Fail. Rev. 10, 225–235 (2005).
    Article CAS PubMed Google Scholar
68. Itoh-Satoh, M., Hayashi, T., Nishi, H., Koga, Y., Arimura, T., Koyanagi, T. et al. Titin mutations as the molecular basis for dilated cardiomyopathy. Biochem. Biophys. Res. Commun. 291, 385–393 (2002).
    Article CAS PubMed Google Scholar
69. Knöll, R., Hoshijima, M., Hoffman, H. M., Person, V., Lorenzen-Schmidt, I., Bang, M. L. et al. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111, 943–955 (2002).
    Article PubMed Google Scholar
70. Zhou, Q., Ruiz-Lozano, P., Martone, M. E. & Chen, J. Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C. J. Biol. Chem. 274, 19807–19813 (1999).
    Article CAS PubMed Google Scholar
71. Frey, N., Richardson, J. A. & Olson, E. N. Calsarcins, a novel family of sarcomeric calcineurin-binding proteins. Proc. Natl. Acad. Sci. USA 97, 14632–14637 (2000).
    Article CAS PubMed PubMed Central Google Scholar
72. Wilkins, B. J. & Molkentin, J. D. Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem. Biophys. Res. Commun. 322, 1178–1191 (2004).
    Article CAS PubMed Google Scholar
73. Heineke, J. & Molkentin, J. D. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nature Rev. Mol. Cell Biol. 7, 589–600 (2006).
    Article CAS Google Scholar
74. Heineke, J., Ruetten, H., Willenbockel, C., Gross, S. C., Naguib, M., Schaefer, A. et al. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc. Proc. Natl. Acad. Sci. USA 102, 1655–1660 (2005).
    Article CAS PubMed PubMed Central Google Scholar
75. Arimura, T., Hayashi, T., Terada, H., Lee, S. Y., Zhou, Q., Takahashi, M. et al. A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C. J. Biol. Chem. 279, 6746–6752 (2004).
    Article CAS PubMed Google Scholar
76. Vatta, M., Mohapatra, B., Jimenez, S., Sanchez, X., Faulkner, G., Perles, Z. et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J. Am. Coll. Cardiol. 42, 2014–2027 (2003).
    Article CAS PubMed Google Scholar
77. Arimura, T., Inagaki, N., Hayashi, T., Shichi, D., Sato, A., Hinohara, K. et al. Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy. Cardiovasc. Res. 83, 80–88 (2009).
    Article CAS PubMed Google Scholar
78. Li, D., Tapscoft, T., Gonzalez, O., Burch, P. E., Quiñones, M. A., Zoghbi, W. A. et al. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation 100, 461–464 (1999).
    Article CAS PubMed Google Scholar
79. Olson, T. M., Illenberger, S., Kishimoto, N. Y., Huttelmaier, S., Keating, M. T. & Jockusch, B. M. Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation 105, 431–437 (2002).
    Article CAS PubMed Google Scholar
80. Taylor, M. R., Slavov, D., Ku, L., Di Lenarda, A., Sinagra, G., Carniel, E. et al. Prevalence of desmin mutations in dilated cardiomyopathy. Circulation 115, 1244–1251 (2007).
    Article CAS PubMed Google Scholar
81. Duboscq-Bidot, L., Xu, P., Charron, P., Neyroud, N., Dilanian, G., Millaire, A. et al. Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy. Cardiovasc. Res. 77, 118–125 (2008).
    Article CAS PubMed Google Scholar
82. Fatkin, D., MacRae, C., Sasaki, T., Wolff, M. R., Porcu, M., Frenneaux, M. et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N. Engl. J. Med. 341, 1715–1724 (1999).
    Article CAS PubMed Google Scholar
83. Bonne, G., Di Barletta, M. R., Varnous, S., Bécane, H. M., Hammouda, E. H., Merlini, L. et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nature Genet. 21, 285–288 (1999).
    Article CAS PubMed Google Scholar
84. Bione, S., Small, K., Aksmanovic, V. M., D’Urso, M., Ciccodicola, A., Merlini, L. et al. Identification of new mutations in the Emery-Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease. Hum. Mol. Genet. 4, 1859–1863 (1995).
    Article CAS PubMed Google Scholar
85. Morris, G. E. & Manilal, S. Heart to heart: from nuclear proteins to Emery-Dreifuss muscular dystrophy. Hum. Mol. Genet. 8, 1847–1851 (1999).
    Article CAS PubMed Google Scholar
86. Sylvius, N. & Tesson, F. Lamin A/C and cardiac diseases. Curr. Opin. Cardiol. 21, 159–165 (2006).
    Article PubMed Google Scholar
87. Arimura, T., Helbling-Leclerc, A., Massart, C., Varnous, S., Niel, F., Lacène, E. et al. Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum. Mol. Genet. 14, 155–169 (2005).
    Article CAS PubMed Google Scholar
88. Muchir, A., Pavlidis, P., Decostre, V., Herron, A. J., Arimura, T., Bonne, G. et al. Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J. Clin. Invest. 117, 1282–1293 (2007).
    Article CAS PubMed PubMed Central Google Scholar
89. Bienengraeber, M., Olson, T. M., Selivanov, V. A., Kathmann, E. C., O’Cochlain, F., Gao, F. et al. ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nature Genet. 36, 382–387 (2004).
    Article CAS PubMed Google Scholar
90. McNair, W. P., Ku, L., Taylor, M. R., Fain, P. R., Dao, D., Wolfel, E. et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation 110, 2163–2167 (2004).
    Article CAS PubMed Google Scholar
91. Lehnart, S. E., Ackerman, M. J., Benson, D. W. Jr., Brugada, R., Clancy, C. E., Donahue, J. K. et al. Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affecting ion channel function. Circulation 116, 2325–2345 (2007).
    Article CAS PubMed Google Scholar
92. Arimura, T., Hayashi, T., Matsumoto, Y., Shibata, H., Hiroi, S., Nakamura, T. et al. Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy. Biochem. Biophys. Res. Commun. 357, 162–167 (2007).
    Article CAS PubMed Google Scholar
93. Johannessen, M., Møller, S., Hansen, T., Moens, U. & Van Ghelue, M. The multifunctional roles of the four-and-a-half-LIM only protein FHL2. Cell Mol. Life Sci. 63, 268–284 (2006).
    Article CAS PubMed Google Scholar
94. Moulik, M., Vatta, M., Witt, S. H., Alora, A. M., Murphy, R. T., McKenna, W. J. et al. ANKRD -the gene encoding cardiac ankyrin repeat protein- is a novel dilated cardiomyopathy gene. J. Am. Coll. Cardiol. 54, 325–333 (2009).
    Article CAS PubMed PubMed Central Google Scholar
95. Hoshijima, M., Knöll, R., Pashmforoush, M. & Chien, K. R. Reversal of calcium cycling defects in advanced heart failure toward molecular therapy. J. Am. Coll. Cardiol. 48, A15–A23 (2006).
    Article CAS PubMed Google Scholar
96. Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U. et al. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 299, 1410–1413 (2003).
    Article CAS PubMed Google Scholar
97. Haghighi, K., Kolokathis, F., Gramolini, A. O., Waggoner, J. R., Pater, L., Lynch, R. A. et al. A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proc. Natl. Acad. Sci. USA 103, 1388–1393 (2006).
    Article CAS PubMed PubMed Central Google Scholar
98. Chiu, C., Tebo, M., Ingles, J., Yeates, L., Arthur, J. W., Lind, J. M. et al. Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy. J. Mol. Cell Cardiol. 43, 337–343 (2007).
    Article CAS PubMed Google Scholar
99. Koss, K. L., Grupp, I. L. & Kranias, E. G. The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility. Basic Res. Cardiol. 92, S17–S24 (1997).
    Article Google Scholar
100. Minamisawa, S., Hoshijima, M., Chu, G., Ward, C. A., Frank, K., Gu, Y. et al. Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99, 313–322 (1999).
     Article CAS PubMed Google Scholar
101. Hoshijima, M., Ikeda, Y., Iwanaga, Y., Minamisawa, S., Date, M. O., Gu, Y. et al. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nature Med. 8, 864–871 (2002).
     Article CAS PubMed Google Scholar
102. Nigro, V., Okazaki, Y., Belsito, A., Piluso, G., Matsuda, Y., Politano, L. et al. Identification of the Syrian hamster cardiomyopathy gene. Hum. Mol. Genet. 6, 601–607 (1997).
     Article CAS PubMed Google Scholar
103. Minamisawa, S., Sato, Y., Tatsuguchi, Y., Fujino, T., Imamura, S., Uetsuka, Y. et al. Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy. Biochem. Biophys. Res. Commun. 304, 1–4 (2003).
     Article CAS PubMed Google Scholar
104. Medin, M., Hermida-Prieto, M., Monserrat, L., Laredo, R., Rodriguez-Rey, J. C., Fernandez, X. et al. Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN-42 C>G mutation. Eur. J. Heart Fail. 9, 37–43 (2007).
     Article CAS PubMed Google Scholar
105. Kadambi, V. J., Ponniah, S., Harrer, J. M., Hoit, B. D., Dorn, G. W. II, Walsh, R. A. et al. Cardiac-specific overexpression of phospholamban alters calcium kinetics and resultant cardiomyocyte mechanics in transgenic mice. J. Clin. Invest. 97, 533–539 (1996).
     Article CAS PubMed PubMed Central Google Scholar
106. Barth, P. G., Valianpour, F., Bowen, V. M., Lam, J., Duran, M., Vaz, F. M. et al. X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update. Am. J. Med. Genet. A 126, 349–354 (2004).
     Article Google Scholar
107. Murakami, T., Hayashi, Y. K., Noguchi, S., Ogawa, M., Nonaka, I., Tanabe, Y. et al. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann. Neurol. 60, 597–602 (2006).
     Article CAS PubMed Google Scholar
108. Norgett, E. E., Hatsell, S. J., Carvajal-Huerta, L., Cabezas, J. C., Common, J., Purkis, P. E. et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum. Mol. Genet. 9, 2761–2766 (2000).
     Article CAS PubMed Google Scholar
109. Uzumcu, A., Norgett, E. E., Dindar, A., Uyguner, O., Nisli, K., Kayserili, H. et al. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome. J. Med. Genet. 43, e5 (2006).
     Article CAS PubMed PubMed Central Google Scholar
110. Arimura, T., Hayashi, Y. K., Murakami, T., Oya, Y., Funabe, S., Hirasawa, E. A. et al. Mutational analysis of fukutin gene in dilated cardiomyopathy and hypertrophic cardiomyopathy. Circ. J. 73, 158–161 (2009).
     Article CAS PubMed Google Scholar
111. Pinto, J. R., Parvatiyar, M. S., Jones, M. A., Liang, J. & Potter, J. D. A troponin T mutation that causes infantile restrictive cardiomyopathy increases Ca2+ sensitivity of force development and impairs the inhibitory properties of troponin. J. Biol. Chem. 283, 2156–2166 (2008).
     Article CAS PubMed Google Scholar
112. Yumoto, F., Lu, Q. W., Morimoto, S., Tanaka, H., Kono, N., Nagata, K. et al. Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy. Biochem. Biophys. Res. Commun. 338, 1519–1526 (2005).
     Article CAS PubMed Google Scholar
113. Kubo, T., Gimeno, J. R., Bahl, A., Steffensen, U., Steffensen, M., Osman, E. et al. Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype. J. Am. Coll. Cardiol. 49, 2419–2426 (2007).
     Article CAS PubMed Google Scholar
114. Mogensen, J., Kubo, T., Duque, M., Uribe, W., Shaw, A., Murphy, R. et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J. Clin. Invest. 111, 209–216 (2003).
     Article CAS PubMed PubMed Central Google Scholar
115. Murphy, R. T., Mogensen, J., Shaw, A., Kubo, T., Hughes, S. & McKenna, W. J. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet 363, 371–372 (2004).
     Article CAS PubMed Google Scholar
116. Budde, B. S., Binner, P., Waldmüller, S., Höhne, W., Blankenfeldt, W., Hassfeld, S. et al. Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene. PLoS ONE 2, e1362 (2007).
     Article PubMed PubMed Central CAS Google Scholar
117. Monserrat, L., Hermida-Prieto, M., Fernandez, X., Rodríguez, I., Dumont, C., Cazón, L. et al. Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects. Eur. Heart J. 28, 1953–1961 (2007).
     Article CAS PubMed Google Scholar
118. Hermida-Prieto, M., Monserrat, L., Castro-Beiras, A., Laredo, R., Soler, R., Peteiro, J. et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am. J. Cardiol. 94, 50–54 (2004).
     Article PubMed Google Scholar
119. Bleyl, S. B., Mumford, B. R., Thompson, V., Carey, J. C., Pysher, T. J., Chin, T. K. et al. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am. J. Hum. Genet. 61, 868–872 (1997).
     Article CAS PubMed PubMed Central Google Scholar
120. Ichida, F., Tsubata, S., Bowles, K. R., Haneda, N., Uese, K., Miyawaki, T. et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation 103, 1256–1263 (2001).
     Article CAS PubMed Google Scholar
121. Chen, H., Shi, S., Acosta, L., Li, W., Lu, J., Bao, S. et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development 131, 2219–2231 (2004).
     Article CAS PubMed Google Scholar
122. Neuhaus, H., Rosen, V. & Thies, R. S. Heart specific expression of mouse BMP-10 a novel member of the TGF-beta superfamily. Mech. Dev. 80, 181–184 (1999).
     Article CAS PubMed Google Scholar
123. Nakano, N., Hori, H., Abe, M., Shibata, H., Arimura, T., Sasaoka, T. et al. Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy. Am. J. Physiol. Heart Circ. Physiol. 293, H3396–H3403 (2007).
     Article CAS PubMed Google Scholar
124. van Tintelen, J. P., Hofstra, R. M., Wiesfeld, A. C., van den Berg, M. P., Hauer, R. N. & Jongbloed, J. D. Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon? Curr. Opin. Cardiol. 22, 185–192 (2007).
     Article PubMed Google Scholar
125. McKoy, G., Protonotarios, N., Crosby, A., Tsatsopoulou, A., Anastasakis, A., Coonar, A. et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355, 2119–2124 (2000).
     Article CAS PubMed Google Scholar
126. Alcalai, R., Metzger, S., Rosenheck, S., Meiner, V. & Chajek-Shaul, T. A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair. J. Am. Coll. Cardiol. 42, 319–327 (2003).
     Article CAS PubMed Google Scholar
127. Gerull, B., Heuser, A., Wichter, T., Paul, M., Basson, C. T., McDermott, D. A. et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nature Genet. 36, 1162–1164 (2004).
     Article CAS PubMed Google Scholar
128. Pilichou, K., Nava, A., Basso, C., Beffagna, G., Bauce, B., Lorenzon, A. et al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation 113, 1171–1179 (2006).
     Article CAS PubMed Google Scholar
129. Tiso, N., Stephan, D. A., Nava, A., Bagattin, A., Devaney, J. M., Stanchi, F. et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum. Mol. Genet. 10, 189–194 (2001).
     Article CAS PubMed Google Scholar
130. Beffagna, G., Occhi, G., Nava, A., Vitiello, L., Ditadi, A., Basso, C. et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc. Res. 65, 366–373 (2005).
     Article CAS PubMed Google Scholar
131. Tadano, N., Morimoto, S., Yoshimura, A., Miura, M., Yoshioka, K., Sakato, M. et al. SCH00013, a novel Ca(2+) sensitizer with positive inotropic and no chronotropic action in heart failure. J. Pharmacol. Sci. 97, 53–60 (2005).
     Article CAS PubMed Google Scholar
132. Arimura, T., Sato, R., Machida, N., Bando, H., Zhang, D. Y., Morimoto, S. et al. Improvement of left ventricular dysfunction and survival prognosis of dilated cardiomyopathy by administration of calcium sensitizer SCH00013 in a mouse model. J. Am. Coll. Cardiol. (in press).

Download references