American Heart Journal
Volume 141, Issue 1 , Page E1 , January 2001

The emerging concept of mitochondrial cardiomyopathies

  • Filippo M. Santorelli, MD

      Affiliations

    • Molecular Medicine, Children’s Hospital “Bambino Gesù,” Rome, Italy
  • ,
  • Alessandra Tessa, PhD

      Affiliations

    • Molecular Medicine, Children’s Hospital “Bambino Gesù,” Rome, Italy
  • ,
  • Giulia d’Amati, MD

      Affiliations

    • Department of Experimental Medicine and Pathology Rome, Italy
  • ,
  • Carlo Casali, MD, PhD

      Affiliations

    • Istituto di Clinica delle Malattie Nervose e Mentali, La Sapienza University, Rome, Italy

Received 11 April 2000 ,Accepted 25 August 2000.

References 

  1. Keating MT, Sanguinetti MC. Molecular genetic insights into cardiovascular disease. Science. 1996;272:681–685
  2. Morris GE, Manilal S. Heart to heart: from nuclear proteins to Emery-Dreifuss muscular dystrophy. Hum Mol Genet. 1999;8:1847–1851
  3. Charron P, Dubourg O, Desnos M, et al.  Genotypephenotype correlations in familial hypertrophic cardiomyopathy: a comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes. Eur Heart J. 1998;19:139–145
  4. DiDonato S. Disorders associated with defects of beta-oxidation. In: 2nd ed.  Rosenberg RN,  Prusiner SB,  DiMauro S, et al. editor. The molecular and genetic basis of neurological disease. Boston: Butterworth-Heinemann; 1997;p. 939–956
  5. Zeviani M, Tiranti V, Piantadosi C. Mitochondrial disorders. Medicine. 1998;77:59–72
  6. Anderson S, Bankier AT, Barrell BG, et al.  Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–465
  7. DiMauro S, Bonilla E. Mitochondrial encephalomyopathies. In: 2nd ed.  Rosenberg R,  Prusiner SB,  DiMauro S, et al. editor. The molecular and genetic basis of neurological disease. Boston: Butterworth-Heinemann; 1997;p. 201–235
  8. Williams R. Cardiac involvement in mitochondrial diseases and vice versa. Circulation. 1995;91:1266–1268
  9. Anan R, Nakagawa M, Miyata M, et al.  Cardiac involvement in mitochondrial diseases: a study of 17 patients with mitochondrial DNA defects. Circulation. 1995;91:955–961
  10. Akaike M, Kawai H, Yokoi K, et al.  Cardiac dysfunction in patients with chronic progressive external ophthalmoplegia. Clin Cardiol. 1997;20:239–243
  11. Pavlakis SG, Phillips PC, DiMauro S, et al.  Mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes: a distinctive clinical syndrome. Ann Neurol. 1984;16:481–488
  12. Hirano M, Pavlakis S. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts. J Child Neurol. 1994;9:4–13
  13. Okajima Y, Tanabe Y, Takayanagi M, et al.  A follow up study of myocardial involvement in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Heart. 1998;80:292–295
  14. Vilarinho L, Santorelli FM, Rosas MJ, et al.  The mitochondrial A3243G mutation presenting as severe cardiomyopathy. J Med Genet. 1997;34:607–609
  15. Zeviani M, Gellera C, Antozzi C, et al.  Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNALeu[UUR]. Lancet. 1991;338:143–147
  16. Silvestri G, Santorelli FM, Shanske S, et al.  A new mtDNA mutation in the tRNA[LeuUUR] gene associated with maternally inherited cardiomyopathy. Hum Mutat. 1994;3:37–43
  17. Bruno C, Kirby DM, Koga Y, et al.  The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy. J Pediatr. 1999;135:197–202
  18. Taniike M, Fukushima H, Yanagihara I, et al.  Mitochondrial tRNA[Ile] mutation in fatal cardiomyopathy. Biochem Biophys Res Commun. 1992;186:47–53
  19. King MP, Attardi G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science. 1989;246:500–503
  20. Hayashi J, Ohta S, Kagawa Y, et al.  Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes. J Biol Chem. 1994;269:19060–19066
  21. Merante F, Myint T, Tein I, et al.  An additional mitochondrial tRNA(Ile) point mutation (A-to-G at nucleotide 4295) causing hypertrophic cardiomyopathy. Hum Mutat. 1996;8:216–222
  22. Casali C, Santorelli FM, d’Amati G, et al.  A novel mtDNA mutation in maternally inherited cardiomyopathy. Biochem Biophys Res Commun. 1995;213:588–593
  23. Casali C, d’Amati G, Bernucci P, et al.  Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid. J Am Coll Cardiol. 1999;33:1584–1589
  24. Shoffner JM, Lott MT, Lezza AM, et al.  Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell. 1990;61:931–937
  25. Hirano M, DiMauro S. Clinical features of mitochondrial myopathies and encephalomyopathies. In:  Lane RJN editors. Handbook of muscle disease. New York: Marcel Dekker; 1996;p. 479–504
  26. Santorelli FM, Mak S-C, El-Schahawi M, et al.  Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial DNA tRNALys gene (G8363A). Am J Hum Genet. 1996;58:933–939
  27. Ozawa M, Nishino I, Horai S, et al.  Myoclonus epilepsy associated with ragged-red fibers: a G-to-A mutation at nucleotide pair 8363 in mitochondrial tRNA(Lys) in two families. Muscle Nerve. 1997;20:271–278
  28. Merante F, Tein I, Benson L, et al.  Maternally inherited hypertrophic cardiomyopathy due to a novel T-to-C transition at nucleotide 9997 in the mitochondrial tRNA(gly) gene. Am J Hum Genet. 1994;55:437–446
  29. Santorelli FM, Tanji K, Manta P, et al.  Maternally inherited cardiomyopathy: an atypical presentation of the mtDNA 12S rRNA gene A1555G mutation. Am J Hum Genet. 1999;64:295–300
  30. Nikoskelainen E, Wanne O, Dahl M. Pre-excitation syndrome and Leber’s hereditary optic neuroretinopathy. Lancet. 1985;1:696
  31. Ortiz RG, Newman NJ, Manoukian SV, et al.  Optic disk cupping and electrocardiographic abnormalities in an American pedigree with Leber’s hereditary optic neuropathy. Am J Ophthalmol. 1992;113:561–566
  32. Marin-Garcia J, Ananthakrishnan R, Korson M, et al.  Cardiac mitochondrial dysfunction in Leigh syndrome. Pediatr Cardiol. 1996;17:387–389
  33. Zeviani M, Petruzzella V, Carrozzo R. Disorders of nuclear-mitochondrial intergenomic signalling. J Bioenerg Biomembr. 1997;29:121–130
  34. Santorelli FM, Hirano M, Shanske S, et al.  Clinical, biochemical, and genetic features of patients with multiple mtDNA deletions. Neurology. 1997;48:A354
  35. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Hypertrophic cardiomyopathy with mitochondrial DNA depletion and respiratory enzyme defects. Pediatr Cardiol. 1998;19:266–268
  36. Li YY, Maisch B, Rose ML, Hengstenberg C. Point mutations in mitochondrial DNA of patients with dilated cardiomyopathy. J Mol Cell Cardiol. 1997;29:2699–2709
  37. Turner LF, Kaddoura S, Harrington D, et al.  Mitochondrial DNA in idiopathic cardiomyopathy. Eur Heart J. 1998;19:1725–1729
  38. Arbustini E, Diegoli M, Fasani R, et al.  Mitochondrial DNA mutations and mitochondrial abnormalities in dilated cardiomyopathy. Am J Pathol. 1998;153:1501–1510
  39. Obayashi T, Hattori K, Sugiyama S, et al.  Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy. Am Heart J. 1992;124:1263–1269
  40. Arbustini E, Fasani R, Morbini P, et al.  Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure. Heart. 1998;80:548–558
  41. Wang J, Wilhelmsson H, Graff C, et al.  Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet. 1999;21:133–137
  42. Muller-Hocker J, Jacob U, Seibel P. The common 4977 base pair deletion of mitochondrial DNA preferentially accumulates in the cardiac conduction system of patients with Kearns-Sayre syndrome. Mod Pathol. 1998;11:295–301
  43. Degoul F, Brulé H, Cepanec C, et al.  Isoleucylation properties of native human mitochondrial tRNAIle and tRNAIle transcripts: implications for cardiomyopathy-related point mutations (4269, 4317) in the tRNAIle gene. Hum Mol Genet. 1998;7:347–354
  44. Graham BH, Waymire KG, Cottrell B, et al.  A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator. Nat Genet. 1997;16:226–234
  45. Rustin P, Lebidois J, Chretien D, et al.  Endomyocardial biopsies for early detection of mitochondrial disorders in hypertrophic cardiomyopathies. J Pediatr. 1994;124:224–228

 Supported in part by Telethon-Italy (grant No. 844 to C. C.) and by grants from the National Research Council and the Italian Ministry of Health.

☆☆ Reprint requests: Filippo M. Santorelli, MD, Molecular Medicine, Children’s Hospital Bambino Gesù, Piazza S. Onofrio, 4 - 00165 Rome, Italy.E-mail: fms3@na.flashnet.it

PII: S0002-8703(01)20623-1

doi: 10.1067/mhj.2001.112088

American Heart Journal
Volume 141, Issue 1 , Page E1 , January 2001