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Advances in Genetics: Dominant Forms

  • Alessandra Rampazzo
  • Gian Antonio Danieli

Abstract

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a progressive cardiomyopathy with different clinical-pathological patterns: (a) “silent” cardiomyopathic abnormalities localized in the right ventricle in asymptomatic victims of sudden death; (b) “overt” disease characterized by segmental or global right ventricular structural changes, often associated with histological evidence of left ventricular involvement and underlying symptomatic ventricular arrhythmias; and (c) “end-stage” biventricular cardiomyopathy mimicking dilated cardiomyopathy, leading to progressive heart failure and eventually requiring heart transplantation [1]. A scoring system to establish the diagnosis of ARVC/D has been developed on the basis of the presence of major and minor criteria encompassing structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease [2].

Keywords

Ventricular Cardiomyopathy Arrhythmogenic Right Ventricular Dysplasia Catecholaminergic Polymorphic Ventricular Tachycardia Desmosomal Protein RYR2 Gene 
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.
    Corrado D, Basso C, Thiene G et al (1997) Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study. J Am Coll Cardiol 30:1512–1520PubMedCrossRefGoogle Scholar
  2. 2.
    McKenna WJ, Thiene G, Nava A et al (1994) Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J 71:215–218PubMedCrossRefGoogle Scholar
  3. 3.
    Thiene G, Nava A, Corrado D et al (1988) Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 318:129–133PubMedCrossRefGoogle Scholar
  4. 4.
    Basso C, Thiene G, Corrado D et al (1996) Arrhythmogenic right ventricular cardiomyopathy. Displasia, dystrophy or myocarditis? Circulation 94:983–991PubMedGoogle Scholar
  5. 5.
    Nava A, Rossi L, Thiene G (eds) (1997) Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Elsevier, AmsterdamGoogle Scholar
  6. 6.
    Marcus FI, Fontaine G, Guiraudon G et al (1982) Right ventricular dysplasia. A report of 24 adult cases. Circulation 65:384–398PubMedGoogle Scholar
  7. 7.
    Nava A, Scognamiglio R, Thiene G et al (1988) Familial occurrence of right ventricular displasia: A study involving nine families. J Am Coll Cardiol 12:1222–1228PubMedCrossRefGoogle Scholar
  8. 8.
    Perzanowski C, Crespo G, Yazdanfar S (2000) Images in cardiology: Familial ventricular tachycardia with mild ventricular dysfunction: A 15-year follow up of two African American brothers with arrhythmogenic right ventricular dysplasia. Heart 84:658PubMedCrossRefGoogle Scholar
  9. 9.
    Fung WH, Sanderson JE (2001) Clinical profile of arrhythmogenic right ventricular cardiomyopathy in Chinese patients. Int J Cardiol 81:9–18PubMedCrossRefGoogle Scholar
  10. 10.
    Obata H, Mitsuoka T, Kikuchi Y et al (2001) Twenty-seven-year follow-up of arrhythmogenic right ventricular dysplasia. Pacing Clin Electrophysiol 24:510–511PubMedCrossRefGoogle Scholar
  11. 11.
    Rampazzo A, Nava A, Danieli GA et al (1994) The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q24. Hum Mol Genet 3:959–962PubMedCrossRefGoogle Scholar
  12. 12.
    Corrado D, Basso C, Schiavon M et al (1998) Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 339:364–369PubMedCrossRefGoogle Scholar
  13. 13.
    Corrado D, Fontaine G, Marcus FI et al (2000) Arrhythmogenic right ventricular dysplasia/cardiomyopathy: Need for an international registry. European Society of Cardiology and the Scientific Council on Cardiomyopathies of the World Heart Federation. J Cardiovasc Electrophysiol 11:827–832PubMedCrossRefGoogle Scholar
  14. 14.
    Marcus F, Towbin JA, Zareba W et al (2003) Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): A multidisciplinary study: Design and protocol. Circulation 107:2975–2978PubMedCrossRefGoogle Scholar
  15. 15.
    Basso C, Wichter T, Danieli GA et al (2004) Arrhythmogenic right ventricular cardiomyopathy: Clinical registry and database, evaluation of therapies, pathology registry, DNA banking. Eur Heart J 25:531–534PubMedCrossRefGoogle Scholar
  16. 16.
    Rampazzo A, Nava A, Erne P et al (1995) A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. Hum Mol Genet 4:2151–2154PubMedCrossRefGoogle Scholar
  17. 17.
    Severini GM, Krajinovic M, Pinamonti B et al (1996) A new locus for arrhythmogenic right ventricular dysplasia on the long arm of chromosome 14. Genomics 31:193–200PubMedCrossRefGoogle Scholar
  18. 18.
    Rampazzo A, Nava A, Miorin M et al (1997) ARVD4, a new locus for arrhythmogenic right ventricular cardiomyopathy, maps to chromosome 2 long arm. Genomics 45:259–263PubMedCrossRefGoogle Scholar
  19. 19.
    Ahmad F, Li D, Karibe A et al (1998) Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation 98:2791–2795PubMedGoogle Scholar
  20. 20.
    Li D, Ahmad F, Gardner MJ et al (2000) The locus of a novel gene responsible for arrhythmogenic right-ventricular dysplasia characterized by early onset and high penetrance maps to chromosome 10p12-p14. Am J Hum Genet 66:148–156PubMedCrossRefGoogle Scholar
  21. 21.
    Melberg A, Oldfors A, Blomstrom-Lundqvist C et al (1999) Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q. Ann Neurol 46:684–692CrossRefGoogle Scholar
  22. 22.
    Rampazzo A, Nava A, Malacrida S et al (2002) Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 71:1200–1206PubMedCrossRefGoogle Scholar
  23. 23.
    Gerull B, Heuser A, Wichter T et al (2004) Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36:1162–1164PubMedCrossRefGoogle Scholar
  24. 24.
    Pilichou K, Nava A, Basso C et al (2006) Mutations in desmoglein-2 gene are associated to arrhythmogenic right ventricular. Circulation 113:1171–1179PubMedCrossRefGoogle Scholar
  25. 25.
    Tiso N, Stephan DA, Nava A et al (2001) Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 10:189–194PubMedCrossRefGoogle Scholar
  26. 26.
    Beffagna G, Occhi G, Nava A et al (2005) Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res 65:366–373PubMedCrossRefGoogle Scholar
  27. 27.
    Stokes DL, Wagenknecht T (2000) Calcium transport across the sarcoplasmic reticulum: Structure and function of Ca2+−ATPase and the ryanodine receptor. Eur J Biochem 267:5274–5279PubMedCrossRefGoogle Scholar
  28. 28.
    Missiaen L, Robberecht W, van den Bosch L et al (2000) Abnormal intracellular ca(2+) homeostasis and disease. Cell Calcium 28:1–21PubMedCrossRefGoogle Scholar
  29. 29.
    Bagattin A, Veronese C, Bauce B et al (2004) Denaturing HPLC-based approach for detecting RYR2 mutations involved in malignant arrhythmias. Clin Chem 50:1148–1155PubMedCrossRefGoogle Scholar
  30. 30.
    Priori SG, Napolitano C, Tiso N et al (2001) Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103:196–200PubMedGoogle Scholar
  31. 31.
    Priori SG, Napolitano C, Memmi M et al (2002) Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 106:69–74PubMedCrossRefGoogle Scholar
  32. 32.
    Laitinen PJ, Brown KM, Piippo K et al (2001) Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103:485–490PubMedGoogle Scholar
  33. 33.
    Laitinen PJ, Swan H, Kontula K (2003) Molecular genetics of exercise-induced polymorphic ventricular tachycardia: Identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms. Eur J Hum Genet 11:888–891PubMedCrossRefGoogle Scholar
  34. 34.
    Kopplin LJ, Tester DJ, Ackerman MJ (2004) Prevalence and spectrum of mutations in the cardiac ryanodine receptor in patients referred for long QT syndrome genetic testing. J Am Coll Cardiol 43:136ACrossRefGoogle Scholar
  35. 35.
    Thomas NL, George CH, Lai FA (2004) Functional heterogeneity of ryanodine receptor mutations associated with sudden cardiac death. Cardiovasc Res 64:52–60PubMedCrossRefGoogle Scholar
  36. 36.
    Leung CL, Green KJ, Liem RK (2002) Plakins: A family of versatile cytolinker proteins. Trends Cell Biol 12:37–45PubMedCrossRefGoogle Scholar
  37. 37.
    Choi HJ, Park-Snyder S, Pascoe LT et al (2002) Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure. Nat Struct Biol 9:612–620PubMedGoogle Scholar
  38. 38.
    Virata ML, Wagner RM, Parry DA et al (1992) Molecular structure of the human desmoplakin I and II amino terminus. Proc Natl Acad Sci USA 89:544–548PubMedCrossRefGoogle Scholar
  39. 39.
    Armstrong DK, McKenna KE, Purkis PE et al (1999) Aploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum Mol Genet 8:143–148PubMedCrossRefGoogle Scholar
  40. 40.
    Whittock NV, Ashton GH, Dopping-Hepenstal PJ et al (1999) Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency. J Invest Dermatol 113:940–946PubMedCrossRefGoogle Scholar
  41. 41.
    Whittock NV, Wan H, Morley SM et al (2002) Compound heterozygosity for non-sense and missense mutations in desmoplakin underlies skin fragility/woolly hair syndrome. J Invest Dermatol 118:232–238PubMedCrossRefGoogle Scholar
  42. 42.
    Norgett EE, Hatsell SJ, Carvajal-Huerta L et al (2000) Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 9:2761–2766PubMedCrossRefGoogle Scholar
  43. 43.
    Alcalai R, Metzger S, Rosenheck S et al (2003) A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair. J Am Coll Cardiol 42:319–327PubMedCrossRefGoogle Scholar
  44. 44.
    Norman M, Simpson M, Mogensen J et al (2005) Novel mutation in desmoplakin causes arrhythmogenic left ventricular cardiomyopathy. Circulation 112:636–642PubMedCrossRefGoogle Scholar
  45. 45.
    Grossmann KS, Grund C, Huelsken J et al (2004) Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. J Cell Biol 167:149–160PubMedCrossRefGoogle Scholar
  46. 46.
    Mertens C, Hofmann I, Wang Z et al (2001) Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin-2. Proc Natl Acad Sci USA 98:7795–7800PubMedCrossRefGoogle Scholar
  47. 47.
    Syrris P, Ward D, Asimaki A et al (2006) Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy. Circulation 113:356–364PubMedCrossRefGoogle Scholar
  48. 48.
    Van Tintelen JP, Entius MM, Bhuiyan ZA et al (2006) Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation 113:1650–1658PubMedCrossRefGoogle Scholar
  49. 49.
    Dalal D, Molin LH, Piccini J et al (2006) Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation 113:1641–1649PubMedCrossRefGoogle Scholar
  50. 50.
    Awad MM, Dalal D, Cho E et al (2006) DSG2 Mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy. Am J Hum Genet 79:136–142PubMedCrossRefGoogle Scholar
  51. 51.
    Rampazzo A, Beffagna G, Nava A et al (2003) Arrhythmogenic right ventricular cardiomyophaty type 1 (ARVD1): Confirmation of locus assignment and mutation screening of four candidate genes. Eur J Hum Gen 11:69–76CrossRefGoogle Scholar
  52. 52.
    Rossi V, Beffagna G, Rampazzo A et al (2004) TAIL1: An isthmin-like gene, containing type 1 thrombospondin-repeat and AMOP domain, mapped to ARVD1 critical region. Gene 335:101–108PubMedCrossRefGoogle Scholar
  53. 53.
    Kapoun AM, Liang F, O’Young G et al (2004) B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: Fibrosis, myofibroblast conversion, proliferation, and inflammation. Circ Res 94:453–61PubMedCrossRefGoogle Scholar
  54. 54.
    Yoshida M, Romberger DJ, Illig MG et al (1992) Transforming growth factor-beta stimulates the expression of desmosomal proteins in bronchial epithelial cells. Am J Respir Cell Mol Biol 6:439–445PubMedGoogle Scholar
  55. 55.
    Ko K, Arora P, Lee W et al (2000) Biochemical and functional characterization of intercellular adhesion and gap junctions in fibroblasts. Am J Physiol Cell Physiol 279:C147–157PubMedGoogle Scholar
  56. 56.
    Gannier D, White E, Garnier F et al (1996) A possible mechanism for large stretch-induced increase in [Ca2+]i in isolated guinea-pig ventricular myocytes. Cardiovasc Res 32:158–167PubMedCrossRefGoogle Scholar
  57. 57.
    Tatsukawa Y, Kiyosue T, Arita M (1997) Mechanical stretch increases intracellular calcium concentration in cultured ventricular cells from neonatal rats. Heart Vessels 12:128–135PubMedGoogle Scholar
  58. 58.
    Knoll R, Hoshijima M, Chien K (2003) Cardiac mechanotransduction and implications for heart disease. J Mol Med 81:750–756PubMedCrossRefGoogle Scholar
  59. 59.
    Petroff MG, Kim SH, Pepe S et al (2001) Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nat Cell Biol 3:867–873PubMedCrossRefGoogle Scholar
  60. 60.
    Beffagna G, De Bortoli M, Nava A et al (2006) Mutations in desmocollin2 gene associated with arrhythmogenic right ventricular cardiomyopathy. Circulation 114:II-723–724Google Scholar
  61. 61.
    Syrris P, Ward D, Evans A et al (2006) Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet 79:978–984PubMedCrossRefGoogle Scholar
  62. 62.
    Henser A, Plovie E, Ellinor PT et al (2006) Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 79:1081–1088CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • Alessandra Rampazzo
    • 1
  • Gian Antonio Danieli
    • 1
  1. 1.Department of BiologyUniversity of PaduaItaly

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