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Genetic Basis of Dilated Cardiomyopathy

  • J. A. Towbin
  • K. R. Bowles
  • R. Ortiz-Lopez
  • Q. Wang
Conference paper

Abstract

Dilated cardiomyopathy (DCM) is a disease of the myocardium characterized by dilation and impaired function of the left ventricle or both ventricles in the absence of coronary artery disease, valvular abnormalities, pericardial disease, and specific myocardial inflammatory diseases including myocarditis [1]. In general, systolic dysfunction is the main clinical feature with resultant signs and symptoms of congestive heart failure. Although the cause of DCM is usually not known, familial transmission is found in some cases. In this manuscript, the current understanding of the genetic causes of DCM is described.

Keywords

Muscular Dystrophy Dilate Cardiomyopathy Duchenne Muscular Dystrophy Myotonic Dystrophy Barth Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies (1996) Circulation 93:841–842CrossRefGoogle Scholar
  2. 2.
    Manolio TA, Baughman KL, Rodenheffer R, Pearson TA, Bristow JD, Michels VV, Abelman WH, Harlan WR (1992) Prevalence and etiology of idiopathic dilated cardiomyopathy (Summary of a National Heart Lung and Blood Institute Workshop). Am J Cardiol 69:1458–1466PubMedCrossRefGoogle Scholar
  3. 3.
    Michels VV, Driscoll DJ, Miller FA Jr. (1985) Familial aggregation of idiopathic dilated cardiomyopathy. Am J Cardiol 55:1232–1233PubMedCrossRefGoogle Scholar
  4. 4.
    Mestroni L, Miani D, DiLenarda A, Silvestri F, Bussani R, Filippi G, Camerini F (1990) Clinical and pathologic study of familial dilated cardiomyopathy. Am J Cardiol 65:1449–1453PubMedCrossRefGoogle Scholar
  5. 5.
    Michels VV, Moll PP, Miller FA, Tajik AJ, Chu JS, Driscoll DJ, Burnett JC, Rodeheffer RJ, Chesebro JH, Tazelaar HD (1992) The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med 326:77–82PubMedCrossRefGoogle Scholar
  6. 6.
    Keeling PJ, Gang Y, Smith G, Seo H, Bent SE, Murday V, Cafario ALP, McKenna WJ (1995) Familial dilated cardiomyopathy in the United Kingdom. Br Heart J 73:417–421PubMedCrossRefGoogle Scholar
  7. 7.
    Gregori D, Rocco C, di Lenarda A, Sinagra G, Miocic S, Camerini F, Mestroni L (1996) Estimating the frequency of familial dilated cardiomyopathy and the risk of misclassification errors. Circulation 94:1–6CrossRefGoogle Scholar
  8. 8.
    Towbin JA (1993) Molecular genetic aspects of cardiomyopathy. Biochem Med Metab Biol 49:285–320PubMedCrossRefGoogle Scholar
  9. 9.
    Neustem HB, Lurie PR, Dahms B, Takahashi M (1979) An X-linked recessive cardiomyopathy with abnormal mitochondria. Pediatrics 64:24–29Google Scholar
  10. 10.
    Barth PG, Scholte HR, Berden JA, Van der Klei-Van Moorsel JM, Luyt-Houwen IEM, Van’T Veer-Korthof ETH, Van der Harten JJ, Sobotka-Plojhar MA (1983) An X-linked mitochondrial disease affecting cardiac muscle skeletal muscle and neutrophil leukocytes. J Neurol Sci 62:327–355PubMedCrossRefGoogle Scholar
  11. 11.
    Kelley RI, Chyeatham JP, Clark BJ, Nigro MA, Powell BR, Sherwood GW, Sladky JT, Swisher WP (1991) X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methyl glutaconic aciduria. J Pediatr 119:738–747PubMedCrossRefGoogle Scholar
  12. 12.
    Berko BA, Swift M (1987) X-linked dilated cardiomyopathy N Engl J Med 316:1186–1191Google Scholar
  13. 13.
    Bolhuis PA, Hensels GW, Hulsebos TJM, 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 48:481–485PubMedGoogle Scholar
  14. 14.
    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. Nature Genet 12:385–389PubMedCrossRefGoogle Scholar
  15. 15.
    Towbin JA, Hejtmancik JF, Brink P, Gelb BD, Zhu XM, Chamberlain JS, McCabe ERB, Swift M (1993) X-linked dilated cardiomyopathy: molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation 87:1854–1865PubMedCrossRefGoogle Scholar
  16. 16.
    Towbin JA (1995) Biochemical and molecular characterization of X-linked dilated cardiomyopathy (XLCM). In: Clark EB, Markwald RR, Takao A (eds) Developmental mechanisms of heart disease. Futura Publishing Co. New York, pp 121–132Google Scholar
  17. 17.
    Muntoni F, Cau M, Ganau A, Congiu R, Arvedi G, Mateddu A, Marrosu MG, Cianchetti C, Realdi G, Cao A, Antonietta M (1993) Brief report: Deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med 329:921–925PubMedCrossRefGoogle Scholar
  18. 18.
    Yoshida K, Ikeda S, Nakamura A, Kagoshima M, Takeda S, Shoji S, Yanagisawa N (1993) Molecular analysis of the Duchenne muscular dystrophy gene in patients with Becker muscular dystrophy presenting with dilated cardiomyopathy. Muscle & Nerve 16:1161–1166CrossRefGoogle Scholar
  19. 19.
    Milasin J, Muntoni F, Severini GM, Bartoloni L, Vatta M, Krajinovic M, Mateddu A, Angelini C, Camerini F, Falaschi A, Mestroni L, Giacca M (1996) A point mutation in the 5’ splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. Hum Mol Genet 5:73–79PubMedCrossRefGoogle Scholar
  20. 20.
    Muntoni F, Wilson L, Marrosu G, Marrosu MG, Cianchetti C, Mestroni L, Ganau A, Dubowitz V, Sewry C (1995) A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart. J Clin Invest 96:693–699PubMedCrossRefGoogle Scholar
  21. 21.
    Ortiz-Lopez R, Su J, Goytia V, Towbin JA (1997) Evidence for a dystrophin missense mutation as a cause of X-linked dilated cardiomyopathy (XLCM). Circulation 95:2434–2440PubMedCrossRefGoogle Scholar
  22. 22.
    Krajinovic M, Pinamonti B, Sinagra G, Vatta M, Severini GM, Milasin J, Filaschi A, Camerini F, Giacca M, Mestroni L (1995) Linkage of familial dilated cardiomyopathy to chromosome 9. Am J Hum Genet 57:846–852PubMedGoogle Scholar
  23. 23.
    Durand J-B, Bachinski LL, Bieling L, Czernuszewicz GZ, Abchee AB, Yu QT, Tapscott T, Hill R, Ifegwu J, Marian AJ, Brugada R, Daiger S, Gregoritch JM, Anderson J, Quinones M, Towbin JA, Roberts R (1995) Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32. Circulation 92:3387–3389PubMedCrossRefGoogle Scholar
  24. 24.
    Bowles KR, Gajarski R, Porter P, Goytia V, Bachinski L, Roberts R, Pignatelli R, Towbin JA (1996) Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23. J Clin Invest 98:1355–1360PubMedCrossRefGoogle Scholar
  25. 25.
    Kass S, MacRae C, Graber HL, Sparks EA, McNamara D, Boudoulas H, Basson CT, Baker PB, Cody RJ, Fishman MC, Cox N, Kong A, Wooley CF, Seidman JG, Seidman CE (1994) A gene defect that causes conduction system disease and dilated cardiomyopathy maps to chromosome 1p1-1q1. Nature Genet 7:546–551PubMedCrossRefGoogle Scholar
  26. 26.
    Olson TM, Keating MT (1996) Mapping a cardiomyopathy locus to chromosome 3p22-p25. J Clin Invest 97:528–532PubMedCrossRefGoogle Scholar
  27. 27.
    Maeda M, Holder E, Lowes B, Bies RD (1997) Dilated cardiomyopathy associated with deficiency of the cytoskeletal protein metavinculin. Circulation 95:17–20PubMedCrossRefGoogle Scholar
  28. 28.
    Fadic R, Sunada Y, Waclawik AJ, Buck S, Lewandoski PJ, Campbell KP, Lotz BP (1996) Brief report: deficiency of a dystrophin-associated glycoprotein (adhalin) in a patient with muscular dystrophy and cardiomyopathy. N Engl J Med 334:362–366PubMedCrossRefGoogle Scholar
  29. 29.
    Ozawa T (1994) Mitochondrial cardiomyopathy. Herz 19:105–118PubMedGoogle Scholar
  30. 30.
    Johns DR (1996) The other human genome: mitochondrial DNA and disease. Nature Med 2:1065–1067PubMedCrossRefGoogle Scholar
  31. 31.
    van der Kooi AJ, Ledderhof TM, de Voogt WG, Res CJ, Bouwsma G, Troost D, Busch HF, Becker AE, de Visser M (1996) A newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21. Ann Neurol 39:636–642PubMedCrossRefGoogle Scholar
  32. 32.
    Malhotra SB, Hart KA, Klamut HJ, Thomas NS, Bodrug SE, Burghes AH, Bobrow M, Harper PS, Thompson MW, Ray PN, Worton RG (1988) Frameshift deletions in patients with Duchenne and Becker muscular dystrophy. Science 242:755–759PubMedCrossRefGoogle Scholar
  33. 33.
    Ahn AH, Kunkel LM (1993) The structural and functional diversity of dystrophin. Nature Genet 3:283–291PubMedCrossRefGoogle Scholar
  34. 34.
    Ozawa E, Yoshida M, Suzuki A, Mizuno Y, Hagiwara Y, Noguchi S (1995) Dystrophinassociated proteins in muscular dystrophy. Hum Mol Genet 4:1711–1716PubMedGoogle Scholar
  35. 35.
    Emery AE (1987) X-linked muscular dystrophy with early contractures and cardiomyopathy (Emery-Dreifuss Type). Clin Genet 32:360–367PubMedCrossRefGoogle Scholar
  36. 36.
    Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D (1994) Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nature Genet 8:323–327PubMedCrossRefGoogle Scholar
  37. 37.
    Towbin JA, Roberts R (1994) Cardiovascular diseases due to genetic abnormalities. In: Schlant RC, Alexander RW (eds) Hurst’s the Heart, Eighth Edition. McGraw-Hill, New York, pp 1725–1759Google Scholar
  38. 38.
    Fu Y-H, Pizzuti A, Fenwick RG, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P, Wieringa B, Korneluk R, Perryman MB, Epstein HF, Caskey CT (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255:1256–1258PubMedCrossRefGoogle Scholar
  39. 39.
    Melacini P, Villanova C, Menegazzo E, Novelli G, Danieli G, Rizzoli G, Fasoli G, Angelini C, Buja G, Miorelli M, Dallapiccola B, Dalla Volta S (1995) Correlation between cardiac involvement and CTG trinucleotide repeat length in myotonic dystrophy. J Am Coll Cardiol 25:239–245PubMedCrossRefGoogle Scholar
  40. 40.
    Schwartz K, Carrier L, Guicheney P, Komajda M (1995) Molecular basis of familial cardiomyopathies. Circulation 91:532–540PubMedCrossRefGoogle Scholar
  41. 41.
    Wang Q, Chen Q, Li H, Towbin JA (1997) Molecular genetics of long QT syndrome: from genes to patients Curr Opinion Cardiol 12:310–320Google Scholar

Copyright information

© Springer-Verlag Italia 1998

Authors and Affiliations

  • J. A. Towbin
  • K. R. Bowles
  • R. Ortiz-Lopez
  • Q. Wang

There are no affiliations available

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