| H00293 | |
| H number | H00293 |
| 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 DIS_PATHWAY hsa05412 Arrhythmogenic right ventricular cardiomyopathy |
| Network | nt06528 Calcium signaling |
| 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] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: BC43.6 ICD-10: I42 OMIM: 107970 600996 604400 607450 609040 610193 610476 611528 615616 618920 |
| Reference | PMID:18001465 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 PMID:17413274 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 PMID:18382419 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 PMID:22426942 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 PMID:15639475 (ARVD1) 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 PMID:11159936 (ARVD2) 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 PMID:18313022 (ARVD5) 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 PMID:12373648 (ARVD8) 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 PMID:15489853 (ARVD9) 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 PMID:16505173 (ARVD10) 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 PMID:17033975 (ARVD11) 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 PMID:17924338 (ARVD12) 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 PMID:23136403 (ARVD13) 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 PMID:28280076 (ARVD14) 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 |