KEGG   DISEASE: Arrhythmogenic right ventricular cardiomyopathy
Entry
H00293                      Disease                                
Name
Arrhythmogenic right ventricular cardiomyopathy
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.
Category
Cardiovascular disease
Brite
Human diseases [BR:br08402]
 Cardiovascular diseases
  Cardiac diseases
   H00293  Arrhythmogenic right ventricular cardiomyopathy
Human diseases in ICD-11 classification [BR:br08403]
 11 Diseases of the circulatory system
  Diseases of the myocardium or cardiac chambers
   BC43  Cardiomyopathy
    H00293  Arrhythmogenic right ventricular cardiomyopathy
Pathway
hsa05412  Arrhythmogenic right ventricular cardiomyopathy
Related
pathway
hsa04260  Cardiac muscle contraction
Gene
(ARVD1) TGFB3 [HSA:7043] [KO:K13377]
(ARVD2) RYR2 [HSA:6262] [KO:K04962]
(ARVD5) TMEM43 [HSA:79188]
(ARVD8) DSP [HSA:1832] [KO:K10381]
(ARVD9) PKP2 [HSA:5318] [KO:K12642]
(ARVD10) DSG2 [HSA:1829] [KO:K07597]
(ARVD11) DSC2 [HSA:1824] [KO:K07601]
(ARVD12) JUP [HSA:3728] [KO:K10056]
(ARVD13) CTNNA3 [HSA:29119] [KO:K05691]
(ARVD14) CDH2 [HSA:1000] [KO:K06736]
Other DBs
ICD-11: BC43.6
ICD-10: I42
OMIM: 107970 600996 604400 607450 609040 610193 610476 611528 615616 618920
Reference
  Authors
Thiene G, Corrado D, Basso C
  Title
Arrhythmogenic right ventricular cardiomyopathy/dysplasia.
  Journal
Orphanet J Rare Dis 2:45 (2007)
DOI:10.1186/1750-1172-2-45
Reference
  Authors
van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD
  Title
Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?
  Journal
Curr Opin Cardiol 22:185-92 (2007)
DOI:10.1097/HCO.0b013e3280d942c4
Reference
  Authors
Awad MM, Calkins H, Judge DP
  Title
Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy.
  Journal
Nat Clin Pract Cardiovasc Med 5:258-67 (2008)
DOI:10.1038/ncpcardio1182
Reference
  Authors
Murray B
  Title
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C): A Review of Molecular and Clinical Literature.
  Journal
J Genet Couns 21:494-504 (2012)
DOI:10.1007/s10897-012-9497-7
Reference
PMID:15639475 (TGFB3)
  Authors
Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, Carraro G, Thiene G, Towbin JA, Danieli GA, Rampazzo A
  Title
Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1.
  Journal
Cardiovasc Res 65:366-73 (2005)
DOI:10.1016/j.cardiores.2004.10.005
Reference
PMID:11159936 (RYR2)
  Authors
Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A
  Title
Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).
  Journal
Hum Mol Genet 10:189-94 (2001)
DOI:10.1093/hmg/10.3.189
Reference
PMID:18313022 (TMEM43)
  Authors
Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL
  Title
Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene.
  Journal
Am J Hum Genet 82:809-21 (2008)
DOI:10.1016/j.ajhg.2008.01.010
Reference
PMID:12373648 (DSP)
  Authors
Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R, Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA
  Title
Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy.
  Journal
Am J Hum Genet 71:1200-6 (2002)
DOI:10.1086/344208
Reference
PMID:15489853 (PKP2)
  Authors
Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L
  Title
Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.
  Journal
Nat Genet 36:1162-4 (2004)
DOI:10.1038/ng1461
Reference
PMID:16505173 (DSG2)
  Authors
Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, Frigo G, Vettori A, Valente M, Towbin J, Thiene G, Danieli GA, Rampazzo A
  Title
Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy.
  Journal
Circulation 113:1171-9 (2006)
DOI:10.1161/CIRCULATIONAHA.105.583674
Reference
PMID:17033975 (DSC2)
  Authors
Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ
  Title
Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2.
  Journal
Am J Hum Genet 79:978-84 (2006)
DOI:10.1086/509122
Reference
PMID:17924338 (JUP)
  Authors
Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ
  Title
A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy.
  Journal
Am J Hum Genet 81:964-73 (2007)
DOI:10.1086/521633
Reference
PMID:23136403 (CTNNA3)
  Authors
van Hengel J, Calore M, Bauce B, Dazzo E, Mazzotti E, De Bortoli M, Lorenzon A, Li Mura IE, Beffagna G, Rigato I, Vleeschouwers M, Tyberghein K, Hulpiau P, van Hamme E, Zaglia T, Corrado D, Basso C, Thiene G, Daliento L, Nava A, van Roy F, Rampazzo A
  Title
Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy.
  Journal
Eur Heart J 34:201-10 (2013)
DOI:10.1093/eurheartj/ehs373
Reference
PMID:28280076 (CDH2)
  Authors
Mayosi BM, Fish M, Shaboodien G, Mastantuono E, Kraus S, Wieland T, Kotta MC, Chin A, Laing N, Ntusi NB, Chong M, Horsfall C, Pimstone SN, Gentilini D, Parati G, Strom TM, Meitinger T, Pare G, Schwartz PJ, Crotti L
  Title
Identification of Cadherin 2 (CDH2) Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy.
  Journal
Circ Cardiovasc Genet 10:e001605 (2017)
DOI:10.1161/CIRCGENETICS.116.001605

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