Progress in Pediatric Cardiology
Volume 25, Issue 1 , Pages 3-21 , April 2008

Molecular mechanisms of pediatric cardiomyopathies and new targeted therapies

  • Jeffrey A. Towbin

      Affiliations

    • Corresponding Author InformationPediatric Cardiology, Baylor College of Medicine, Texas Children's Hospital, 6621 Fannin Street, MC 19345-C, Houston, TX 77030 USA. Tel.: +1 832 826 5651; fax: +1 832 825 5921.

References 

  1. Towbin JA, Bowles NE. Cardiomyopathy. In:  McMillian JA,  Feigin RA,  DeAngelis CD,  Jones MD editor. Oski's Pediatrics. Principles & Practice. 4th Edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2005;p. 1624–1648Chapter 283
  2. Abelman WH, Lorrell BH. The challenge of cardiomyopathy. J Am Coll Cardiol. 1989;13:1219
  3. Towbin JA. Hypertrophic Cardiomyopathy. 2005. In: Heart Failure in Children and Young Adults. From Molecular Mechanisms to Medical and Surgical Strategies. Chang AC, Towbin JA, editors. Saunders Elsevier, Inc., Philadelphia, PA, 2006, Chapter 20, pp. 278–297.
  4. Towbin JA, Bowles NE. The failing heart. Nature. 2002;415:227–233
  5. Morita H, Seidman CE. Genetic causes of human heart failure. J Clin Invest. 2005;115:518–526
  6. Maron BJ, Towbin JA, Thiene G, et al. American Heart Association Council on Clinical Cardiology, Heart Failure and Transplantation Committee Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups Council on Epidemiology and Prevention 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
  7. Schwartz SM, Duffy JY, Pearl JM, Nelson DP. Cellular and molecular aspects of myocardial dysfunction. 2001;29:S214–S219.
  8. Gregorio CC, Antin PB. To the heart of myofibril assembly. Trends Cell Biol. 2000;10:355–362
  9. Clark KA, McElhinny AS, Beckerle MC, Gregorio CC. Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol. 2002;18:637–706
  10. Vigoreaux JO. The muscle Z band: lessons in stress management. J Muscle Res Cell Motil. 1994;15:237–255
  11. Barth AL, Nathke IS, Nelson WJ. Cadherins, catenins and APC protein; interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol. 1997;9:683–690
  12. Capetanaki Y. Desmin cytoskeleton: a potential regulator of muscle mitochondrial behaviour and function. Trends Cardiovasc Med. 2002;12:339–348
  13. Sharp WW, Simpson DG, Borg TK, Samarel AM, Terracio L. Mechanical forces regulate focal adhesion and costamere assembly in cardiac myocytes. Am J Physiol. 1997;273:H546–H556
  14. Straub V, Campbell KP. Muscular dystrophies and the dystrophin-glycoprotein complex. Curr Opin Neurol. 1997;10:168–175
  15. Furukawa T, Ono Y, Tsuchiya H, et al. 2001. Specific interaction of the potassium channel beta-subunit iph with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system. 313:775–784.
  16. Kucera JP, Rohr S, Rudy Y. Localization of sodium channels in intercalated disks modulates cardiac conduction. Circ Res. 2002;91:1176–1182
  17. Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcome of dilated cardiomyopathy. JAMA. 2006;296:1867–1876
  18. Michels VV, Moll PP, Miller FA, et al. The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992;326:77–82
  19. Berko BA, Swift M. X-linked dilated cardiomyopathy. N Engl J Med. 1987;316:1186–1191
  20. Towbin JA, Bowles KR, Bowles NE. Etiologies cardiomyopathy and heart failure. Nat Med. 1999;5:266–267
  21. Towbin JA, Hejtmancik JF, Brink P, et al. X-linked dilated cardiomyopathy (XLCM): Molecular genetic evidence of linkage to the Duchenne muscular dystrophy gene at the Xp21 locus. Circulation. 1993;87:1854–1865
  22. Muntoni F, Cau M, Ganau A, et al. Brief report: deletion of the dystrophin muscle-specific promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med. 1993;329:921–925
  23. Cox GF, Kunkel LM. Dystrophies and heart disease. Curr Opin Cardiol. 1997;12:329–343
  24. Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987;51:919–928
  25. Meng H, Leddy JJ, Frank J, Holland P, Tuana BS. The association of cardiac dystrophin with myofibrils/z-discs regions in cardiac muscle suggests a novel role in the contractile apparatus. J Biol Chem. 1996;271:12364–12371
  26. Kaprielian RR, Stevenson S, Rothery SM, Cullen MJ, Severs NJ. Distinct patterns of dystrophin organization in myocyte sarcolemma and transverse tubules of normal and diseased human myocardium. Circulation. 2000;101:2586–2594
  27. Koenig M, Hoffman EP, Bertelson CJ, et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987;50:509–517
  28. Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeny HL. Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A. 1993;90:3710–3714
  29. Campbell KP. Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell. 1995;80:675–679
  30. Klietsch R, Ervasti JM, Arnold W, Campbell KP, Jorgensen AO. Dystrophin-glycoprotein complex and laminin colocalize to the sarcolemma and transverse tubules of cardiac muscle. Circ Res. 1993;72:349–360
  31. Ozawa E, Yoshida M, Suzuki A, Mizuno Y, Hagiwara Y, Noguchi S. Dystrophin-associated proteins in muscular dystrophy. Hum Mol Genet. 1995;4:1711–1716
  32. Emery AE. The muscular dystrophies. Lancet. 2002;359:687–695
  33. Davies KE, Nowak KJ. Molecular mechanisms of muscular dystrophies: old and new players. Nat Rev Mol Cell Biol. 2006;7:762–773
  34. Towbin JA. The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol. 1998;10:131–139
  35. Bowles NE, Bowles KR, Towbin JA. The “Final Common Pathway” hypothesis and inherited cardiovascular disease: the role of cytoskeletal proteins in dilated cardiomyopathy. Herz. 2000;25:168–175
  36. Feng J, Yan J, Buzin CH, Towbin JA, Sommer SS. Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. Mol Genet Metab. 2002;77:119–126
  37. Feng J, Yan J, Buzin CH, Sommer SS, Towbin JA. Comprehensive mutation scanning of the dystrophin gene in patients with nonsyndromic X-linked dilated cardiomyopathy. J Am Coll Cardiol. 2002;40:1120–1124
  38. Neustein HD, Lurie PR, Dahms B, Takahashi M. An X-linked recessive cardiomyopathy with abnormal mitochondria. Pediatrics. 1979;64:24–29
  39. Barth PG, Scholte HR, Berden JA, et al. An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci. 1983;62:327–355
  40. Kelley RI, Cheatham JP, Clark BJ, et al. X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria. J Pediatr. 1991;119:738–747
  41. Schlame M, Towbin JA, Heerdt PM, Jehle R, DiMauro S, Blanck TJJ. Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome. Ann Neurol. 2002;51:634–637
  42. Bione S, D'Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D. A novel X-linked gene, G4.5, is responsible for Barth syndrome. Nat Genet. 1996;12:385–389
  43. Bleyl SB, Mumford BR, Thompson V, et al. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet. 1997;61:868–872
  44. Graber HL, Unverferth DV, Baker PB, Ryan JM, Baba N, Wooley CF. Evolution of hereditary cardiac conduction and muscle disorder: a study involving a family with 6 generations affected. Circulation. 1986;74:21–35
  45. Tsubata S, Bowles KR, Vatta M, et al. Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J Clin Invest. 2000;106:655–662
  46. Karkkainen S, Peuhkurinen K. Genetics of dilated cardiomyopathy. Ann Med. 2007;32:91–107
  47. Towbin JA, Bowles NE. Dilated cardiomyopathy: a tale of the cytoskeleton and beyond. J Cardiovasc Electrophysiol. 2006;17:919–926
  48. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998;280:750–752
  49. Kamisago M, Sharma SD, DePalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000;343:1688–1696
  50. Li D, Tapscott T, Gonzalez O, et al. Desmin mutations responsible for idiopathic dilated cardiomyopathy. Circulation. 1999;100:461–464
  51. Fatkin D, Graham RM. Molecular mechanisms of inherited cardiomyopathies. Physiol Rev. 2002;82:945–980
  52. Ozawa E, Mizumo Y, Hagiwara Y, Sasaoka T, Yoshida M. Molecular and cellular biology of the sarcoglycan complex. Muscle Nerve. 2005;32:563–576
  53. Coral-Vazquez R, Cohn RD, Moore SA, et al. Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell. 1999;98:465–474
  54. Wheeler MT, Allikian MJ, Heydemann A, Hadhazy M, Zarnegar S, McNally EM. Smooth muscle cell-extrinsic vascular spasms arise from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy. J Clin Invest. 2004;113:668–675
  55. Sakamoto A, Ono K, Abe M, et al. Both hypertrophic and dilated cardiomyopathies are caused by mutation of the same gene, delta-sarcoglycan, in hamster: an animal model of disrupted dystrophin-associated glycoprotein complex. Proc Natl Acad Sci U S A. 1997;94:13873–13878
  56. Olson TM, Illenberger S, Kishimoto NY, Huttelmaier S, Keating MT, Jockusch BM. Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation. 2002;105:431–437
  57. Maeda M, Holder E, Lowes B, Valent S, Bies RD. Dilated cardiomyopathy associated with deficiency of the cytoskeletal protein metavinculin. Circulation. 1997;95:17–20
  58. Chang AN, Potter JD. Sarcomeric protein mutations in dilated cardiomyopathy. Heart Fail Rev. 2005;10:225–235
  59. Schmitt JP, Kamisago M, Asahi M, et al. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. 2003;299:1410–1413
  60. Haghighi K, Kolokathis F, Pater L, et al. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J Clin Invest. 2003;111:869–876
  61. Murphy RT, Mogensen J, Shaw A, et al. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet. 2004;363:371–372
  62. Olson TM, Kishimoto NY, Whitby FG, Michels VV. Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy. J Mol Cell Cardiol. 2001;33:723–732
  63. Pyle WG, Solaro RJ. At the crossroads of myocardial signaling: the role of Z-discs in intracellular signaling and cardiac function. Circ Res. 2004;94:296–305
  64. Knoll R, Hoshijima M, Hoffman HM, et al. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 2002;11:943–955
  65. Arber S, Hunter JJ, Ross J, et al. MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell. 1997;88:393–403
  66. Zolk O, Caroni P, Bohm M. Decreased expression of the cardiac LIM domain protein MLP in chronic human heart failure. Circulation. 2000;101:2674–2677
  67. Katz AM. Cytoskeletal abnormalities in the failing heart. Out on a LIM?. Circulation. 2000;101:2672–2673
  68. Zhou Q, Chu PH, Huang C, et al. Ablation of cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy. J Cell Biol. 2001;155:605–612
  69. Granzier H, Labeit S. The grant protein titin: a major player in myocardial mechanics, signaling, and disease. Circ Res. 2004;94:284–295
  70. Gerul B, Gramlich M, Atherton J, et al. Mutations of TTN encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet. 2002;30:201–204
  71. Fatkin D, MacRae C, Sasaki T, 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. 1999;34:1715–1724
  72. Brodsky GL, Muntoni F, Miocic S, Sinagra G, Sewry C, Mestroni L. Lamin A./C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation. 2000;101:473–476
  73. Stuurman N, Heins S, Aebi U. Nuclear lamins: their structure, assembly and interactions. J Struct Biol. 1998;122:42–66
  74. Bonne G, DiBarletta MR, Varnous S, et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery–Dreifuss muscular dystrophy. Nat Genet. 1999;21:285–288
  75. Di Barletta R, Ricci E, Galluzzi G, et al. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery–Dreifuss muscular dystrophy. Am J Hum Genet. 2000;66:1407–1412
  76. Muchir A, Bonne G, van der Kooi AJ, et al. Identification of mutations in the gene encoding lamin A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbance (LGMD1B). Hum Mol Genet. 2000;9:1453–1459
  77. Decostre V, Ben Yaou R, Bonne G. Laminopathies affecting skeletal and cardiac muscles: clinical and pathological aspects. Acta Myol. 2005;24:104–109
  78. Taylor MR, Slavov D, Gajewski A, Vlcek S, Ku L, Fain PR, et al. Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy. Hum Mutat. 2005;26:566–574
  79. Badorff C, Lee G-H, Lamphear BJ, et al. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med. 1999;5:320–326
  80. Xiong D, Lee GH, Badorff C, et al. Dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy: a genetic predisposition to viral heart disease. Nat Med. 2002;8:872–877
  81. Vatta M, Stetson SJ, Perez-Verdra A, et al. Molecular remodeling of dystrophin in patients with end-stage cardiomyopathies and reversal for patients on assist device therapy. Lancet. 2000;359:936–941
  82. Vatta M, Stetson SJ, Jimenez S, et al. Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices. J Am Coll Cardiol. 2004;43:811–817
  83. Maron BJ. Hypertrophic cardiomyopathy: a systemic review. JAMA. 2002;287:1308–1320
  84. Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet. 2004;363:188–189
  85. Colan SD, Lipshultz SE, Lowe AM, et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation. 2007;115:773–781
  86. McKenna WJ, Behr ER. Hypertrophic cardiomyopathy: management, risk stratification, and prevention of sudden death. Heart. 2002;87:169–176
  87. Frenneaux MP. Assessing the risk of sudden cardiac death in a patient with hypertrophic cardiomyopathy. Heart. 2004;90:570–575
  88. Maron BJ, Carney KP, Lever HM, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2003;41:974–980
  89. Maron BJ. Hypertrophic cardiomyopathy and sudden death: new perspective on risk stratification and prevention with the implantable cardioverter–defibrillator. Eur Heart J. 2000;21:1979–1983
  90. Spirito P, Maron BJ, Bonow RO, Epstein SE. Occurrence and significance of progressive left ventricular wall thinning and relative cavity dilation in hypertrophic cardiomyopathy. Am J Cardiol. 1987;60:123–139
  91. Aurigemma GP, Gaasch WH. Diastolic heart failure. N Engl J Med. 2004;351:1097–1105
  92. Gaasch WH, Zile MR. Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med. 2004;55:373–394
  93. Towbin JA, Lipshultz SE. Genetics of neonatal cardiomyopathy. Curr Opin Cardiol. 1999;14:250–262
  94. Vulpian A. Contribution à l'étude des rétrécissements de l'orifice ventriculo-aortique. Arch Physiol. 1868;3:220–222
  95. Watkins H. Genetic clues to disease pathways in hypertrophic and dilated cardiomyopathies. Circulation. 2003;107:1344–1346
  96. Jarcho JA, McKenna W, Pare JA, et al. Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. N Engl J Med. 1989;321:1372–1378
  97. Solomon SD, Jarcho JA, McKenna WJ, et al. Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease. J Clin Invest. 1990;86:993–999
  98. Watkins H, MacRae C, Thierfelder L, et al. A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. Nat Genet. 1993;3:333–337
  99. Thierfelder L, MacRae C, Watkins H, et al. A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2. Proc Natl Acad Sci U S A. 1993;90:6270–6274
  100. Carrier L, Hengstenberg C, Beckmann JS, et al. Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11. Nat Genet. 1993;4:311–313
  101. MacRae CA, Ghaisas N, Kass S, et al. Familial hypertrophic cardiomyopathy with Wolff–Parkinson–White Syndrome maps to a locus on chromosome 7q3. J Clin Invest. 1995;96:1216–1220
  102. Poetter K, Jiang H, Hassanzadeh S, et al. Mutation in either the essential regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet. 1996;13:63–69
  103. Kimura A, Harada H, Park JE, et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet. 1997;16:379–382
  104. Mogensen J, Klausen IC, Pederson AK, et al. α-Cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J Clin Invest. 1999;103:R39–R43
  105. 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. 1999;2625:411–417
  106. Geier C, Perrot A, Ozcelik C, et al. Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy. Circulation. 2003;107:1390–1395
  107. Mohiddin SA, Ahmed ZM, Griffith AJ, et al. Novel association of hypertrophic cardiomyopathy, sensorineural deafness and a mutation in unconventional myosin VI (MYO6). J Med Genet. 2004;41:309–314
  108. Hayashi T, Armimura T, Ueda K, et al. Identification and functional and of caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2004;313:178–184
  109. Seidman JG, Seidman C. The genetic basis for cardiomyopathy from mutation identification to mechanistic paradigms. Cell. 2001;108:557–567
  110. Towbin JA, Bowles NE. The failing heart. Nature. 2002;415:227–233
  111. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371–423
  112. Gollob MH, Green MS, Tang AS, et al. Identification of a gene responsible for familial Wolff–Parkinson–White syndrome. N Engl J Med. 2001;344:1823–1831
  113. Blair E, Redwood C, Ashrafian H, et al. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for a central role of energy compromise in disease pathogenesis. Hum Mol Genet. 2001;10:1215–1220
  114. Arad M, Benson DW, Perez-Atayde AR, et al. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest. 2002;107:357–362
  115. Blair E, Redwood C, de Jesus Oliveira M, et al. Mutations of the light meromyosin domain of the β-myosin heavy chain rod in hypertrophic cardiomyopathy. Circ Res. 2002;90:263–269
  116. 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
  117. Lees-Miller JP, Helfman DM. The molecular basis for tropomyosin isoform diversity. Bioessays. 1991;13:429–437
  118. Mesnard L, Logeart D, Taviaux S, Diriong S, Mercadier JJ, Samson F. Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart. Circ Res. 1995;76:687–692
  119. Townsend P, Barton P, Yacoub M, Farza H. Molecular cloning of human cardiac troponin T isoforms: expression in developing and failing heart. J Mol Cell Cardiol. 1995;27:2223–2236
  120. Hunkeler NM, Kullman J, Murphy AM. Troponin I isoform expression in human heart. Circ Res. 1991;69:1409–1414
  121. Theis JL, Bos JM, Bartleson VB, et al. Echocardiography-determined septal morphology in Z-disc hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006;351:896–902
  122. Osio A, Tan L, Chen SN, et al. Myozenin-2 is a novel gene for human hypertrophic cardiomyopathy. Circ Res. 2007;100:766–768
  123. Watkins H, Rosenzweig T, Hwang DS, et al. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992;326:1108–1114
  124. Moolman JC, Corfield VA, Posen B, et al. Sudden death due to troponin T mutations. J Am Coll Cardiol. 1997;29:549–555
  125. 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. 1997;29:839–843
  126. Bonne G, Carrier L, Bercovici J, et al. Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nat Genet. 1995;11:438–440
  127. Watkins H, Conner D, Thierfelder L, et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet. 1995;11:434–437
  128. Niimura H, Bachinski LL, Sangwatanaroj S, et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med. 1998;338:1248–1257
  129. Charron P, Dubourg O, Desnos M, et al. Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to cardiac myosin-binding protein C gene. Circulation. 1998;97:2230–2236
  130. Van Driest SL, Ackerman MJ, Ommen SR, et al. Prevalence and severity of “benign” mutations in the β-myosin heavy chain, cardiac troponin T, and α-tropomyosin genes in hypertrophic cardiomyopathy. Circulation. 2002;106:3085–3090
  131. Yoneya K, Okamoto H, Machida M, et al. Angiotensin-converting enzyme gene polymorphism in Japanese patients with hypertrophic cardiomyopathy. Am Heart J. 1995;130:1089–1093
  132. Tesson F, Dufour C, Moolman JC, et al. The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation. J Mol Cell Cardiol. 1997;29:831–838
  133. Ortlepp JR, Vosberg HP, Reith S, et al. Genetic polymorphisms in the rennin–angiotensin–aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Heart. 2002;87:270–275
  134. Doiuchi J, Hamada M, Ito T, Kokubu T. Comparative effects of calcium-channel blockers and beta-adrenergic blocker on early diastolic time intervals and A-wave ratio in patients with hypertrophic cardiomyopathy. Clin Cardiol. 1987;10:26–30
  135. Lorell BH. Use of calcium channel blockers in hypertrophic cardiomyopathy. Am J Med. 1985;78:43–54
  136. Moran AM, Colan SD. Verapamil therapy in infants with hypertrophic cardiomyopathy. Cardiol Young. 1998;8:310–319
  137. Nagueh SF, Ommen SR, Lakkis NM, et al. Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2001;38:1701–1706
  138. Maron BJ, Dearani JA, Ommen SR, et al. The case for surgery in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 44:2043–2053.
  139. O'Rourke RA. Cardiac pacing. An alternative treatment for selected patients with hypertrophic cardiomyopathy and adjunctive therapy for certain patients with dilated cardiomyopathy. Circulation. 1999;100:786–788
  140. Maron BJ. Appraisal of dual-chamber pacing therapy in hypertrophic cardiomyopathy: too soon for a rush to judgment?. J Am Coll Cardiol. 1996;27:431–432
  141. Begley D, Mohiddin S, Fananapazir L. Dual chamber pacemaker therapy for mid-cavity obstructive hypertrophic cardiomyopathy. Pacing Clin Electrophysiol. 2001;24:1639–1644
  142. Chang SM, Lakkis NM, Franklin J, Spencer WH, Nagueh SF. Predictors of outcome after alcohol septal ablation therapy in patients with hypertrophic obstructive cardiomyopathy. Circulation. 2004;109:824–827
  143. Nielsen CD, Killip D, Spencer WH. Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: short-term results in 50 consecutive procedures. Clin Cardiol. 2003;26:275–279
  144. Park TH, Lakkis NM, Middleton KJ, et al. Acute effect of nonsurgical septal reduction therapy on regional left ventricular asynchrony in patients with hypertrophic obstructive cardiomyopathy. Circulation. 2002;106:412–415
  145. Hess OM, Sigwart U. New treatment strategies for hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2004;44:2054–2055
  146. Cable WJ, Kolodny EH, Adams RD. Fabry disease: impaired autonomic function. Neurology. 1982;32:498–502
  147. Sugie K, Yamamoto A, Murayama K, et al. Clinicopathological features of genetically confirmed Danon disease. Neurology. 2002;58:1773–1778
  148. Yang Z, McMahon CJ, Smith LR, et al. Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation. Sep 13 2005;112(11):1612–1617
  149. Hers HG, van Hoof F, de Barsy T. Glycogen storage diseases. In:  Scriver CR,  Beaudet AL,  Sly WS,  Valle D editor. The Metabolic Basis of Inherited Disease. 6th Ed.. New York: McGraw-Hill; 1989;p. 425–452
  150. Towbin JA. Molecular genetic aspects of cardiomyopathy. Biochem Med Metab Biol. 1993;49:283–320
  151. D'Ancona GG, Wurm J, Croce CM. Genetics of type II glycogenosis: assignment of the human gene for acid α-glucosidase to chromosome 17. Proc Natl Acad Sci U S A. 1979;76:4526–4529
  152. Beratis NG, LaBadie GU, Hirschhorn K. Genetic heterogeneity in acid α-glucosidase deficiency. Am J Hum Genet. 1983;35:21–33
  153. Zhong N, Martiniuk F, Tzall S, Hirschhorn R. Identification of a missense mutation in one allele of a patient with Pompe disease and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele. Am J Hum Genet. 1991;49:635–645
  154. Raben N, Danon M, Gilbert AL, et al. Enzyme replacement therapy in the mouse model of Pompe disease. Mol Genet Metab. 2003;80:159–169
  155. Masson C, Cisse I, Simon V, Insalaco P, Audran M. Fabry disease: a review. Joint Bone Spine. 2004;71:381–383
  156. Colucci WS, Lorell BH, Schoen FJ, Warhol MJ, Grossman W. Hypertrophic obstructive cardiomyopathy due to Fabry's disease. N Engl J Med. 1982;307:926–928
  157. Becker AE, Schoorl R, Balk AG, van der Heide RM. Cardiac manifestations of Fabry's disease: report of a case with mitral insufficiency and electrocardiographic evidence of myocardial infarction. Am J Cardiol. 1975;36:829–835
  158. Goldman ME, Cantor R, Schwartz MF, Baker M, Desnick RJ. Echocardiographic abnormalities and disease severity in Fabry's disease. J Am Coll Cardiol. 1986;7:1157–1161
  159. Broadbent JC, Edwards WD, Gordon H, Hartzler GO, Krawisz JE. Fabry cardiomyopathy in the female confirmed by endomyocardial biopsy. Mayo Clin Proc. 1981;56:623–628
  160. Bishop DF, Calhoun DH, Bernstein HS, Hantzopoulos P, Quinn M, Desnick RJ. Human alpha galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. Proc Natl Acad Sci U S A. 1986;83:4859–4863
  161. Eng CM, Desnick RJ. Molecular basis of Fabry disease. Mutations and polymorphisms in the human α-galactosidase A gene. Hum Mutat. 1994;3:103–111
  162. Okumiya T, Ishii S, Kase R, Sakuraba H, Suzuki Y. α-galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins. Hum Genet. 1995;95:557–561
  163. Nakao S, Takenaka T, Maeda M, et al. An atypical variant of Fabry's disease in men with left ventricular hypertrophy. N Engl J Med. 1995;333:288–293
  164. Linhart A, Palecek T, Bultas J , et al. New insights in cardiac structural changes in patients with Fabry's disease. Am Heart J. 2000;139:1101–1108
  165. Sachdev B, Takenaka T, Teraguchih H, et al. Prevalence of Anderson–Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation. 2002;105:1407–1411
  166. Danon MJ, Oh SJ, DiMauro S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology. 1981;31:51–57
  167. Nishino I, Fu J, Tanji K, et al. Primary LAMP-2 deficiency causes X-linked vascular cardiomyopathy and myopathy (Danon Disease). Nature. 2000;406:906–909
  168. Charron P, Villard E, Sebillon P, et al. Danon's disease as a cause of hypertrophic cardiomyopathy: A systematic survey. Heart 90:842–846.
  169. Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J. 2000;346:659–669
  170. Kemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, Witters LA. Dealing with energy demand: the AMP-activated protein kinase. Trends Biochem Sci. 1999;24:22–25
  171. Arad M, Moskowitz IP, Patel VV, et al. Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff Parkinson–White syndrome in glycogen storage cardiomyopathy. Circulation. 2003;107:2850–2856
  172. Attardi G. The elucidation of the human mitochondrial genome: a historical perspective. Bioessays. 1996;5:34–39
  173. Wallace DC, Zheng X, Lott MT, et al. Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell. 1988;55:601–610
  174. Wallace DC. Mitochondrial DNA mutation and neuromuscular disease. Trends Genet. 1989;5:9–13
  175. Clarke A. Mitochondrial genome: defects, disease, and evolution. J Med Genet. 1990;27:451–456
  176. Grivell LA. Small, beautiful and essential. Nature. 1989;341:569–571
  177. Anderson S, Banker AT, Barrell BG. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–465
  178. Petty RKH, Harding AE, Morgan-Hughes JA. The clinical features of mitochondrial myopathy. Brain. 1986;109:915–938
  179. Mariotti C, Tiranti V, Carrara F, Dallapiccola B, DiDonato S, Zeviani M. Defective respiratory capacity and mitochondrial protein synthesis in transformant cybrids harboring the tRNALeu(UUR) mutation associated with maternally inherited myopathy and cardiomyopathy. J Clin Invest. 1994;93:1102–1107
  180. Vogel H. Mitochondrial myopathies and the role of the pathologist in the molecular era. J Neuropathol Exp Neurol. 2001;60:217–227
  181. Capaldi RA, Halphen DG, Zhang YZ, Yanamura W. Complexity and tissue specificity of the mitochondrial respiratory chain. J Bioenerg Biomembr. 1988;20:291–311
  182. Ozawa T, Tanaka M, Sugiyama S, et al. Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy. Biochem Biophys Res Commun. 1990;170:830–836
  183. Scaglia F, Towbin JA, Craigen WJ, et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics. 2004;114:925–931
  184. Channer KD, Channer JL, Campbell MJ, Rees JR. Cardiomyopathy in Kearns–Sayre syndrome. Br Heart J. 1988;59:486–490
  185. Poulton J, Deadman ME, Ramacharan S, Gardiner RM. Germ-line deletions of mtDNA in mitochondrial myopathy. Am J Hum Genet. 1991;48:649–653
  186. CT Moraes, S DiMauro, M Zeviani, et-al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns–Sayre syndrome, N Engl J Med, 320, 1293–1299.
  187. Moraes CT, Schon EA, DiMauro S, Miranda AF. Heteroplasmy of mitochondrial genomes in clonal cultures from patients with Kearns–Sayre syndrome. Biochem Biopsy Res Commun. 1989;160:765–771
  188. Suomalainen A, Kollmann P, Octave J-N, Soderlund H, Syvanen AC. Quantification of mitochondrial DNA carrying tRNA8344Lys point mutation in myoclonus epilepsy and ragged-red fiber disease. Eur J Hum Genet. 1993;1:88–95
  189. Tanno Y, Yoneda M, Nonaka I, Tanaka K, Miyatake T, Tsuji S. Quantitation of mitochondrial DNA carrying tRANLys mutation in MERRF patients. Biochem Biophys Res Commun. 1991;179:880–885
  190. Shoffner JM, Lott MI, Lezza AM, Seibel P, Ballinger SW, Wallace DC. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell. 1990;61:931–937
  191. Nakamura M, Nakano S, Goto Y, et al. A novel point mutation in the mitochondrial tRNASer(UCN) gene detected in a family with MERFF/MELAS overlap syndrome. Biochem Biophys Res Commun. 1995;214:86–93
  192. Silvestri G, Moraes CT, Shanske S, Oh SJ, DiMauro S. A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and ragged-red fibers (MERRF). Am J Hum Genet. 1992;51:1213–1217
  193. Fukuhara N. Clinicopathologic features of MERRF. Muscle Nerve. 1995;3:590–594J Pediatr 124:224–228
  194. Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical characterization of left ventricular noncompaction in children. A relatively common form of cardiomyopathy. Circulation. 2003;108:2672–2678
  195. 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
  196. Stollberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol. 2002;90:899–902
  197. Stollberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction. J Am Soc Echocardiogr. 2004;17:91–100
  198. Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of isolated noncompaction of the ventricular myocardium: long-term clinical course, hemodynamic properties and genetic background. J Am Coll Cardiol. 1999;34:233–240
  199. Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001;103:1256–1263
  200. Vatta M, Mohapatra B, Jimenez S, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol. 2003;42:2014–2027

PII: S1058-9813(07)00162-2

doi: 10.1016/j.ppedcard.2007.11.001

Progress in Pediatric Cardiology
Volume 25, Issue 1 , Pages 3-21 , April 2008

Article Tools

* Image Usage & Resolution