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Nuclear Genes Causing Mitochondrial Cardiomyopathy

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Mitochondrial Disorders Caused by Nuclear Genes

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Abstract

The heart is one of the major energy-consuming organs. Consequently, cardiac muscle dysfunction is a common but underrecognized feature of mitochondrial disease. Patients with mitochondrial disease and cardiac involvement have higher morbidity and mortality. Early recognition and prompt treatment of cardiac symptoms can significantly impact recovery and limit disease progression. Mutations in the X-linked gene TAZ cause Barth syndrome, a disorder characterized by dilated cardiomyopathy, neutropenia, growth retardation, and 3-methlyglutaconic aciduria. An undulating cardiac phenotype is common in many mitochondrial cardiomyopathies including Barth syndrome, with phenotypes alternating between hypertrophic and dilated forms. Left ventricular noncompaction, a developmental arrest of the myocardium, may be seen in isolation or in combination with other cardiomyopathy phenotypes. Four additional nuclear genes known to cause mitochondrial cardiomyopathy by disparate mechanisms are SLC25A3, SURF1, SCO2, and TMEM70. In addition, secondary cardiac mitochondrial dysfunction is a common finding in patients with end-stage heart failure, aging, ischemia, and diabetes. Consequently, there is substantial interest in the identification of therapy for both primary and secondary cardiac mitochondrial dysfunction.

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References

  1. Clark KA, McElhinny AS, Beckerle MC, Gregorio CC (2002) Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol 18:637–706

    Article  PubMed  CAS  Google Scholar 

  2. Luther PK (2009) The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling. J Muscle Res Cell Motil 30:171–185

    Article  PubMed  Google Scholar 

  3. Gregorio CC, Antin PB (2000) To the heart of myofibril assembly. Trends Cell Biol 10:355–362

    Article  PubMed  CAS  Google Scholar 

  4. Pyle WG, Solaro RJ (2004) At the crossroads of myocardial signaling: the role of Z-discs in intracellular signaling and cardiac function. Circ Res 94:296–305

    Article  PubMed  CAS  Google Scholar 

  5. Ventura-Clapier R, Garnier A, Veksler V, Joubert F (2011) Bioenergetics of the failing heart. Biochim Biophys Acta 1813:1360–1372

    Article  PubMed  CAS  Google Scholar 

  6. Lehman JJ, Kelly DP (2002) Transcriptional activation of energy metabolic switches in the developing and hypertrophied heart. Clin Exp Pharmacol Physiol 29:339–345

    Article  PubMed  CAS  Google Scholar 

  7. Fisher DJ, Heymann MA, Rudolph AM (1981) Myocardial consumption of oxygen and carbohydrates in newborn sheep. Pediatr Res 15:843–846

    Article  PubMed  CAS  Google Scholar 

  8. Lai L, Leone TC, Zechner C, Schaeffer PJ, Kelly SM, Flanagan DP, Medeiros DM, Kovacs A, Kelly DP (2008) Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev 22:1948–1961

    Article  PubMed  CAS  Google Scholar 

  9. Hansson A, Hance N, Dufour E, Rantanen A, Hultenby K, Clayton DA, Wibom R, Larsson NG (2004) A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts. Proc Natl Acad Sci U S A 101:3136–3141

    Article  PubMed  CAS  Google Scholar 

  10. Pejznochova M, Tesarova M, Hansikova H, Magner M, Honzik T, Vinsova K, Hajkova Z, Havlickova V, Zeman J (2010) Mitochondrial DNA content and expression of genes involved in mtDNA transcription, regulation and maintenance during human fetal development. Mitochondrion 10:321–329

    Article  PubMed  CAS  Google Scholar 

  11. Taegtmeyer H (2002) Switching metabolic genes to build a better heart. Circulation 106:2043–2045

    Article  PubMed  Google Scholar 

  12. Taegtmeyer H, Razeghi P, Young ME (2002) Mitochondrial proteins in hypertrophy and atrophy: a transcript analysis in rat heart. Clin Exp Pharmacol Physiol 29:346–350

    Article  PubMed  CAS  Google Scholar 

  13. Ingwall JS, Weiss RG (2004) Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 95:135–145

    Article  PubMed  CAS  Google Scholar 

  14. Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356:1140–1151

    Article  PubMed  Google Scholar 

  15. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129

    Article  PubMed  CAS  Google Scholar 

  16. Crouser ED (2004) Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome. Mitochondrion 4:729–741

    Article  PubMed  CAS  Google Scholar 

  17. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) 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

    Article  PubMed  Google Scholar 

  18. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kuhl U, Maisch B, McKenna WJ et al (2008) Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 29:270–276

    Article  PubMed  Google Scholar 

  19. Towbin JA (2010) Left ventricular noncompaction: a new form of heart failure. Heart Fail Clin 6:453–469, viii

    Article  PubMed  Google Scholar 

  20. Munnich A, Rustin P (2001) Clinical spectrum and diagnosis of mitochondrial disorders. Am J Med Genet 106:4–17

    Article  PubMed  CAS  Google Scholar 

  21. Wolf NI, Smeitink JA (2002) Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology 59:1402–1405

    Article  PubMed  Google Scholar 

  22. Bernier FP, Boneh A, Dennett X, Chow CW, Cleary MA, Thorburn DR (2002) Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 59:1406–1411

    Article  PubMed  CAS  Google Scholar 

  23. Morava E, Van den Heuvel L, Hol F, De Vries MC, Hogeveen M, Rodenburg RJ, Smeitink JA (2006) Mitochondrial disease criteria: diagnostic applications in children. Neurology 67:1823–1826

    Article  PubMed  CAS  Google Scholar 

  24. Scaglia F, Towbin JA, Craigen WJ, Belmont JW, Smith EO, Neish SR, Ware SM, Hunter JV, Fernbach SD, Vladutiu GD et al (2004) Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 114:925–931

    Article  PubMed  Google Scholar 

  25. Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M (2003) Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J 24:280–288

    Article  PubMed  CAS  Google Scholar 

  26. Colan SD, Lipshultz SE, Lowe AM, Sleeper LA, Messere J, Cox GF, Lurie PR, Orav EJ, Towbin JA (2007) Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation 115:773–781

    Article  PubMed  Google Scholar 

  27. Cox GF, Sleeper LA, Lowe AM, Towbin JA, Colan SD, Orav EJ, Lurie PR, Messere JE, Wilkinson JD, Lipshultz SE (2006) Factors associated with establishing a causal diagnosis for children with cardiomyopathy. Pediatr 118:1519–1531

    Article  Google Scholar 

  28. Kindel SJ, Miller EM, Gupta R, Cripe LH, Hinton RB, Spicer RL, Towbin JA, Ware SM (2012) Pediatric cardiomyopathy: importance of genetic and metabolic evaluation. J Card Fail 18(5):396–403

    Article  PubMed  CAS  Google Scholar 

  29. Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, Cox GF, Lurie PR, Hsu D et al (2006) Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 296:1867–1876

    Article  PubMed  CAS  Google Scholar 

  30. Daubeney PE, Nugent AW, Chondros P, Carlin JB, Colan SD, Cheung M, Davis AM, Chow CW, Weintraub RG (2006) Clinical features and outcomes of childhood dilated cardiomyopathy: results from a national population-based study. Circulation 114:2671–2678

    Article  PubMed  Google Scholar 

  31. Barth PG, Scholte HR, Berden JA, Van der Klei-Van Moorsel JM, Luyt-Houwen IE, Van ’t Veer-Korthof ET, Van der Harten JJ, Sobotka-Plojhar MA (1983) An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci 62:327–355

    Article  PubMed  CAS  Google Scholar 

  32. Bione S, D’Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D (1996) A novel X-linked gene, G4.5. is responsible for Barth syndrome. Nat Genet 12:385–389

    CAS  Google Scholar 

  33. Bleyl SB, Mumford BR, Thompson V, Carey JC, Pysher TJ, Chin TK, Ward K (1997) Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet 61:868–872

    Article  PubMed  CAS  Google Scholar 

  34. D’Adamo P, Fassone L, Gedeon A, Janssen EA, Bione S, Bolhuis PA, Barth PG, Wilson M, Haan E, Orstavik KH et al (1997) The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. Am J Hum Genet 61:862–867

    Article  PubMed  Google Scholar 

  35. Orstavik KH, Orstavik RE, Naumova AK, D’Adamo P, Gedeon A, Bolhuis PA, Barth PG, Toniolo D (1998) X chromosome inactivation in carriers of Barth syndrome. Am J Hum Genet 63:1457–1463

    Article  PubMed  CAS  Google Scholar 

  36. Kelley RI, Cheatham JP, Clark BJ, Nigro MA, Powell BR, Sherwood GW, Sladky JT, Swisher WP (1991) X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria. J Pediatr 119:738–747

    Article  PubMed  CAS  Google Scholar 

  37. Cardonick EH, Kuhlman K, Ganz E, Pagotto LT (1997) Prenatal clinical expression of 3-methylglutaconic aciduria: Barth syndrome. Prenat Diagn 17:983–988

    Article  PubMed  CAS  Google Scholar 

  38. Steward CG, Newbury-Ecob RA, Hastings R, Smithson SF, Tsai-Goodman B, Quarrell OW, Kulik W, Wanders R, Pennock M, Williams M et al (2010) Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth. Prenat Diagn 30:970–976

    Article  PubMed  CAS  Google Scholar 

  39. Adwani SS, Whitehead BF, Rees PG, Morris A, Turnball DM, Elliott MJ, De Leval MR (1997) Heart transplantation for Barth syndrome. Pediatr Cardiol 18:143–145

    Article  PubMed  CAS  Google Scholar 

  40. Mangat J, Lunnon-Wood T, Rees P, Elliott M, Burch M (2007) Successful cardiac transplantation in Barth syndrome—single-centre experience of four patients. Pediatr Transplant 11:327–331

    Article  PubMed  Google Scholar 

  41. Mazzocco MM, Kelley RI (2001) Preliminary evidence for a cognitive phenotype in Barth syndrome. Am J Med Genet 102:372–378

    Article  PubMed  CAS  Google Scholar 

  42. Schlame M, Kelley RI, Feigenbaum A, Towbin JA, Heerdt PM, Schieble T, Wanders RJ, DiMauro S, Blanck TJ (2003) Phospholipid abnormalities in children with Barth syndrome. J Am Coll Cardiol 42:1994–1999

    Article  PubMed  CAS  Google Scholar 

  43. Hauff KD, Hatch GM (2006) Cardiolipin metabolism and Barth syndrome. Prog Lipid Res 45:91–101

    Article  PubMed  CAS  Google Scholar 

  44. Gohil VM, Hayes P, Matsuyama S, Schagger H, Schlame M, Greenberg ML (2004) Cardiolipin biosynthesis and mitochondrial respiratory chain function are interdependent. J Biol Chem 279:42612–42618

    Article  PubMed  CAS  Google Scholar 

  45. Sparagna GC, Lesnefsky EJ (2009) Cardiolipin remodeling in the heart. J Cardiovasc Pharmacol 53:290–301

    Article  PubMed  CAS  Google Scholar 

  46. Gebert N, Joshi AS, Kutik S, Becker T, McKenzie M, Guan XL, Mooga VP, Stroud DA, Kulkarni G, Wenk MR et al (2009) Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome. Curr Biol 19:2133–2139

    Article  PubMed  CAS  Google Scholar 

  47. Valianpour F, Mitsakos V, Schlemmer D, Towbin JA, Taylor JM, Ekert PG, Thorburn DR, Munnich A, Wanders RJ, Barth PG et al (2005) Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis. J Lipid Res 46:1182–1195

    Article  PubMed  CAS  Google Scholar 

  48. Valianpour F, Wanders RJ, Barth PG, Overmars H, Van Gennip AH (2002) Quantitative and compositional study of cardiolipin in platelets by electrospray ionization mass spectrometry: application for the identification of Barth syndrome patients. Clin Chem 48:1390–1397

    PubMed  CAS  Google Scholar 

  49. Chicco AJ, Sparagna GC (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol 292:C33–C44

    Article  PubMed  CAS  Google Scholar 

  50. Houtkooper RH, Turkenburg M, Poll-The BT, Karall D, Perez-Cerda C, Morrone A, Malvagia S, Wanders RJ, Kulik W, Vaz FM (2009) The enigmatic role of tafazzin in cardiolipin metabolism. Biochim Biophys Acta 1788:2003–2014

    Article  PubMed  CAS  Google Scholar 

  51. Sparagna GC, Chicco AJ, Murphy RC, Bristow MR, Johnson CA, Rees ML, Maxey ML, McCune SA, Moore RL (2007) Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure. J Lipid Res 48:1559–1570

    Article  PubMed  CAS  Google Scholar 

  52. Russell LK, Finck BN, Kelly DP (2005) Mouse models of mitochondrial dysfunction and heart failure. J Mol Cell Cardiol 38:81–91

    Article  PubMed  CAS  Google Scholar 

  53. Saini-Chohan HK, Holmes MG, Chicco AJ, Taylor WA, Moore RL, McCune SA, Hickson-Bick DL, Hatch GM, Sparagna GC (2009) Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure. J Lipid Res 50:1600–1608

    Article  PubMed  CAS  Google Scholar 

  54. Erkkila A, De Mello VD, Riserus U, Laaksonen DE (2008) Dietary fatty acids and cardiovascular disease: an epidemiological approach. Prog Lipid Res 47:172–187

    Article  PubMed  CAS  Google Scholar 

  55. Chicco AJ, Sparagna GC, McCune SA, Johnson CA, Murphy RC, Bolden DA, Rees ML, Gardner RT, Moore RL (2008) Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat diets. Hypertension 52:549–555

    Article  PubMed  CAS  Google Scholar 

  56. Acehan D, Vaz F, Houtkooper RH, James J, Moore V, Tokunaga C, Kulik W, Wansapura J, Toth MJ, Strauss A et al (2011) Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J Biol Chem 286:899–908

    Article  PubMed  CAS  Google Scholar 

  57. Khuchua Z, Yue Z, Batts L, Strauss AW (2006) A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function. Circ Res 99:201–208

    Article  PubMed  CAS  Google Scholar 

  58. Xu Y, Condell M, Plesken H, Edelman-Novemsky I, Ma J, Ren M, Schlame M (2006) A Drosophila model of Barth syndrome. Proc Natl Acad Sci U S A 103:11584–11588

    Article  PubMed  CAS  Google Scholar 

  59. Malhotra A, Edelman-Novemsky I, Xu Y, Plesken H, Ma J, Schlame M, Ren M (2009) Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome. Proc Natl Acad Sci U S A 106 2337–2341

    Article  PubMed  CAS  Google Scholar 

  60. Dolce V, Iacobazzi V, Palmieri F, Walker JE (1994) The sequences of human and bovine genes of the phosphate carrier from mitochondria contain evidence of alternatively spliced forms. J Biol Chem 269:10451–10460

    PubMed  CAS  Google Scholar 

  61. Huizing M, Ruitenbeek W, Van den Heuvel LP, Dolce V, Iacobazzi V, Smeitink JA, Palmieri F, Trijbels JM (1998) Human mitochondrial transmembrane metabolite carriers: tissue distribution and its implication for mitochondrial disorders. J Bioenerg Biomembr 30:277–284

    Article  PubMed  CAS  Google Scholar 

  62. Mayr JA, Merkel O, Kohlwein SD, Gebhardt BR, Bohles H, Fotschl U, Koch J, Jaksch M, Lochmuller H, Horvath R et al (2007) Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. Am J Hum Genet 80:478–484

    Article  PubMed  CAS  Google Scholar 

  63. Bohm M, Pronicka E, Karczmarewicz E, Pronicki M, Piekutowska-Abramczuk D, Sykut-Cegielska J, Mierzewska H, Hansikova H, Vesela K, Tesarova M et al (2006) Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. Pediatr Res 59:21–26

    Article  PubMed  Google Scholar 

  64. Sacconi S, Salviati L, Sue CM, Shanske S, Davidson MM, Bonilla E, Naini AB, De Vivo DC, DiMauro S (2003) Mutation screening in patients with isolated cytochrome c oxidase deficiency. Pediatr Res 53:224–230

    Article  PubMed  CAS  Google Scholar 

  65. Moslemi AR, Darin N (2007) Molecular genetic and clinical aspects of mitochondrial disorders in childhood. Mitochondrion 7:241–252

    Article  PubMed  CAS  Google Scholar 

  66. Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum, DM et al (1999) Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nat Genet 23:333–337

    Article  PubMed  CAS  Google Scholar 

  67. Cizkova A, Stranecky V, Mayr JA, Tesarova M, Havlickova V, Paul J, Ivanek R, Kuss AW, Hansikova H, Kaplanova V et al (2008) TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. Nat Genet 40:1288–1290

    Article  PubMed  CAS  Google Scholar 

  68. Sperl W, Jesina P, Zeman J, Mayr JA, Demeirleir L, VanCoster R, Pickova A, Hansikova H, Houst’kova H, Krejcik Z et al (2006) Deficiency of mitochondrial ATP synthase of nuclear genetic origin. Neuromuscul Disord 16:821–829

    Article  PubMed  CAS  Google Scholar 

  69. Wortmann SB, Rodenburg RJ, Jonckheere A, De Vries MC, Huizing M, Heldt K, Van den Heuvel LP, Wendel U, Kluijtmans LA, Engelke UF et al (2009) Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy. Brain 132:136–146

    Article  PubMed  Google Scholar 

  70. Shchelochkov OA, Li FY, Wang J, Zhan H, Towbin JA, Jefferies JL, Wong LJ, Scaglia F (2010) Milder clinical course of type IV 3-methylglutaconic aciduria due to a novel mutation in TMEM70. Mol Genet Metab 101:282–285

    Article  PubMed  CAS  Google Scholar 

  71. Spiegel R, Khayat M, Shalev SA, Horovitz Y, Mandel H, Hershkovitz E, Barghuti F, Shaag A, Saada A, Korman SH et al (2011) TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome. J Med Genet 48:177–182

    Article  PubMed  Google Scholar 

  72. Ware SM, El-Hassan N, Kahler SG, Zhang Q, Ma YW, Miller E, Wong B, Spicer RL, Craigen WJ, Kozel BA et al (2009) Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes. J Med Genet 46:308–314

    Article  PubMed  CAS  Google Scholar 

  73. Schon EA, Santra S, Pallotti F, Girvin ME (2001) Pathogenesis of primary defects in mitochondrial ATP synthesis. Semin Cell Dev Biol 12:441–448

    Article  PubMed  CAS  Google Scholar 

  74. Houstek J, Pickova A, Vojtiskova A, Mracek T, Pecina P, Jesina P (2006) Mitochondrial diseases and genetic defects of ATP synthase. Biochim Biophys Acta 1757:1400–1405

    Article  PubMed  CAS  Google Scholar 

  75. Cameron JM, Levandovskiy V, Mackay N, Ackerley C, Chitayat D, Raiman J, Halliday WH, Schulze A, Robinson BH (2011) Complex V TMEM70 deficiency results in mitochondrial nucleoid disorganization. Mitochondrion 11:191–199

    Article  PubMed  CAS  Google Scholar 

  76. Hejzlarova K, Tesarova M, Vrbacka-Cizkova A, Vrbacky M, Hartmannova H, Kaplanova V, Noskova L, Kratochvilova H, Buzkova J, Havlickova V et al (2011) Expression and processing of the TMEM70 protein. Biochim Biophys Acta 1807:144–149

    Article  PubMed  CAS  Google Scholar 

  77. Marin-Garcia J, Goldenthal MJ (2002) Understanding the impact of mitochondrial defects in cardiovascular disease: a review. J Card Fail 8:347–361

    Article  PubMed  CAS  Google Scholar 

  78. Taegtmeyer H, McNulty P, Young ME (2002) Adaptation and maladaptation of the heart in diabetes: part I: general concepts. Circulation 105:1727–1733

    Article  PubMed  CAS  Google Scholar 

  79. Thompson CH, Kemp GJ, Taylor DJ, Conway M, Rajagopalan B, O’Donoghue A, Styles P, McKenna WJ, Radda GK (1997) Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy. Heart 78:177–181

    PubMed  CAS  Google Scholar 

  80. Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y (2000) Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J Cell Biol 150:1283–1298

    Article  PubMed  CAS  Google Scholar 

  81. Bowles NE, Bowles KR, Towbin JA (2000) The “final common pathway” hypothesis and inherited cardiovascular disease. The role of cytoskeletal proteins in dilated cardiomyopathy. Herz 25:168–175

    Article  PubMed  CAS  Google Scholar 

  82. Vatta M, Stetson SJ, Perez-Verdia A, Entman ML, Noon GP, Torre-Amione G, Bowles NE, Towbin JA (2002) Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies and reversal in patients on assistance-device therapy. Lancet 359936–359941

    Google Scholar 

  83. Azevedo VM, Albanesi Filho FM, Santos MA, Castier MB, Cunha MO (2005) The role of L-carnitine in nutritional status and echocardiographic parameters in idiopathic dilated cardiomyopathy in children. J Pediatr (Rio J) 81:368–372

    Google Scholar 

  84. Langsjoen PH, Vadhanavikit S, Folkers K (1985) Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. Proc Natl Acad Sci U S A 82:4240–4244

    Article  PubMed  CAS  Google Scholar 

  85. Lerman-Sagie T, Rustin P, Lev D, Yanoov M, Leshinsky-Silver E, Sagie A, Ben-Gal T, Munnich A (2001) Dramatic improvement in mitochondrial cardiomyopathy following treatment with idebenone. J Inherit Metab Dis 24:28–34

    Article  PubMed  CAS  Google Scholar 

  86. Bhagavan HN, Chopra RK (2005) Potential role of ubiquinone (coenzyme Q10) in pediatric cardiomyopathy. Clin Nutr 24:331–338

    Article  PubMed  CAS  Google Scholar 

  87. Watson PS, Scalia GM, Galbraith A, Burstow DJ, Bett N, Aroney CN (1999) Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol 33:1549–1552

    Article  PubMed  CAS  Google Scholar 

  88. Bolhuis PA, Hensels GW, Hulsebos TJ, Baas F, Barth PG (1991) Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28. Am J Hum Genet 48:481–485

    PubMed  CAS  Google Scholar 

  89. Durr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M (1996) Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med 335:1169–1175

    Article  PubMed  CAS  Google Scholar 

  90. Dutka DP, Donnelly JE, Nihoyannopoulos P, Oakley CM, Nunez DJ (1999) Marked variation in the cardiomyopathy associated with Friedreich’s ataxia. Heart 81:141–147

    PubMed  CAS  Google Scholar 

  91. Dutka DP, Donnelly JE, Palka P, Lange A, Nunez DJ, Nihoyannopoulos P (2000) Echocardiographic characterization of cardiomyopathy in Friedreich’s ataxia with tissue Doppler echocardiographically derived myocardial velocity gradients. Circulation 102:1276–1282

    Article  PubMed  CAS  Google Scholar 

  92. Isnard R, Kalotka H, Durr A, Cossee M, Schmitt M, Pousset F, Thomas D, Brice A, Koenig M, Komajda M (1997) Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreich’s ataxia. Circulation 95:2247–2249

    Article  PubMed  CAS  Google Scholar 

  93. Buchaklian AH, Helbling D, Ware SM, Dimmock DP (2012) Recessive deoxyguanosine kinase deficiency causes juvenile onset mitochondrial myopathy. Mol Genet Metab (in press) (PMID: 22715278)

    Google Scholar 

  94. Palmieri L, Alberio S, Pisano I, Lodi T, Meznaric-Petrusa M, Zidar J, Santoro A, Scarcia P, Fontanesi F, Lamantea E et al (2005) Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum Mol Genet 14:3079–3088

    Article  PubMed  CAS  Google Scholar 

  95. Echaniz-Laguna A, Chassagne M, Ceresuela J, Rouvet I, Padet S, Acquaviva C, Nataf S, Vinzio S, Bozon D, Mousson de Camaret B (2012) Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy. J Med Genet 49:146–150

    Article  PubMed  CAS  Google Scholar 

  96. Honzik T, Tesarova M, Mayr JA, Hansikova H, Jesina P, Bodamer O, Koch J, Magner M, Freisinger P, Huemer M et al (2010) Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation. Arch Dis Child 95:296–301

    Article  PubMed  Google Scholar 

  97. Holme E, Greter J, Jacobson CE, Larsson NG, Lindstedt S, Nilsson KO, Oldfors A, Tulinius M (1992) Mitochondrial ATP-synthase deficiency in a child with 3-methylglutaconic aciduria. Pediatr Res 32:731–735

    Article  PubMed  CAS  Google Scholar 

  98. Mayr JA, Paul J, Pecina P, Kurnik P, Forster H, Fotschl U, Sperl W, Houstek J (2004) Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase. Pediatr Res 55:988–994

    Article  PubMed  CAS  Google Scholar 

  99. Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA (2003) Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. Hum Mol Genet 12:2693–2702

    Article  PubMed  CAS  Google Scholar 

  100. Antonicka H, Mattman A, Carlson CG, Glerum DM, Hoffbuhr KC, Leary SC, Kennaway NG, Shoubridge EA (2003) Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am J Hum Genet 72:101–114

    Article  PubMed  CAS  Google Scholar 

  101. Benit P, Beugnot R, Chretien D, Giurgea I, De Lonlay-Debeney P, Issartel JP, Corral-Debrinski M, Kerscher S, Rustin P, Rotig A et al (2003) Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy. Hum Mutat 21:582–586

    Article  PubMed  CAS  Google Scholar 

  102. Berger I, Hershkovitz E, Shaag A, Edvardson S, Saada A, Elpeleg O (2008) Mitochondrial complex I deficiency caused by a deleterious NDUFA11 mutation. Ann Neurol 63:405–408

    Article  PubMed  CAS  Google Scholar 

  103. Loeffen J, Elpeleg O, Smeitink J, Smeets R, Stockler-Ipsiroglu S, Mandel H, Sengers R, Trijbels F, Van den Heuvel L (2001) Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalomyopathy. Ann Neurol 49:195–201

    Article  PubMed  CAS  Google Scholar 

  104. Loeffen J, Smeitink J, Triepels R, Smeets R, Schuelke M, Sengers R, Trijbels F, Hamel B, Mullaart R, Van den Heuvel L (1998) The first nuclear-encoded complex I mutation in a patient with Leigh syndrome. Am J Hum Genet 63:1598–1608

    Article  PubMed  CAS  Google Scholar 

  105. Levitas A, Muhammad E, Harel G, Saada A, Caspi VC, Manor E, Beck JC, Sheffield V, Parvari R (2010) Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Eur J Hum Genet 18:1160–1165

    Article  PubMed  CAS  Google Scholar 

  106. Smeitink JA, Elpeleg O, Antonicka H, Diepstra H, Saada A, Smits P, Sasarman F, Vriend G, Jacob-Hirsch J, Shaag A et al (2006) Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs. Am J Hum Genet 79:869–877

    Article  PubMed  CAS  Google Scholar 

  107. Saada A, Shaag A, Arnon S, Dolfin T, Miller C, Fuchs-Telem D, Lombes A, Elpeleg O (2007) Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. J Med Genet 44:784–786

    Article  PubMed  CAS  Google Scholar 

  108. Smits P, Saada A, Wortmann SB, Heister AJ, Brink M, Pfundt R, Miller C, Haas D, Hantschmann R, Rodenburg RJ et al (2011) Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange-like phenotype, brain abnormalities and hypertrophic cardiomyopathy. Eur J Hum Genet 19:394–399

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, 240 Albert Sabin Way, MLC 7020 USA, 45229, Cincinnati, OH, USA

    Stephanie M. Ware MD, PhD & Jeffrey A. Towbin MD

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  1. Stephanie M. Ware MD, PhD
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  2. Jeffrey A. Towbin MD
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Correspondence to Stephanie M. Ware MD, PhD .

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  1. , Dept. of Molecular and Human Genetics, Baylor College of Medicine, Baylor Plaza ONE, Houston, 77030, Texas, USA

    Lee-Jun C. Wong

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Ware, S., Towbin, J. (2013). Nuclear Genes Causing Mitochondrial Cardiomyopathy. In: Wong, LJ. (eds) Mitochondrial Disorders Caused by Nuclear Genes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3722-2_20

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