| H00293 | |
| H番号 | H00293 |
| 名称 | 不整脈源性右室心筋症 |
| 概要 | 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. |
| カテゴリ | 循環器系疾患 疾患パスウェイ hsa05412 不整脈源性右室心筋症 |
| ネットワーク | nt06528 Calcium signaling |
| 病因遺伝子 | (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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | - |
| コメント | - |
| リンク | ICD-11: BC43.6 ICD-10: I42 OMIM: 107970 600996 604400 607450 609040 610193 610476 611528 615616 618920 |
| 文献 | PMID:18001465 著者 Thiene G, Corrado D, Basso C タイトル Arrhythmogenic right ventricular cardiomyopathy/dysplasia. 雑誌 Orphanet J Rare Dis 2:45 (2007) DOI:10.1186/1750-1172-2-45 PMID:17413274 著者 van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD タイトル Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon? 雑誌 Curr Opin Cardiol 22:185-92 (2007) DOI:10.1097/HCO.0b013e3280d942c4 PMID:18382419 著者 Awad MM, Calkins H, Judge DP タイトル Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. 雑誌 Nat Clin Pract Cardiovasc Med 5:258-67 (2008) DOI:10.1038/ncpcardio1182 PMID:22426942 著者 Murray B タイトル Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C): A Review of Molecular and Clinical Literature. 雑誌 J Genet Couns 21:494-504 (2012) DOI:10.1007/s10897-012-9497-7 PMID:15639475 (ARVD1) 著者 Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, Carraro G, Thiene G, Towbin JA, Danieli GA, Rampazzo A タイトル Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. 雑誌 Cardiovasc Res 65:366-73 (2005) DOI:10.1016/j.cardiores.2004.10.005 PMID:11159936 (ARVD2) 著者 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 タイトル Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). 雑誌 Hum Mol Genet 10:189-94 (2001) DOI:10.1093/hmg/10.3.189 PMID:18313022 (ARVD5) 著者 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 タイトル Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. 雑誌 Am J Hum Genet 82:809-21 (2008) DOI:10.1016/j.ajhg.2008.01.010 PMID:12373648 (ARVD8) 著者 Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R, Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA タイトル Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. 雑誌 Am J Hum Genet 71:1200-6 (2002) DOI:10.1086/344208 PMID:15489853 (ARVD9) 著者 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 タイトル Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. 雑誌 Nat Genet 36:1162-4 (2004) DOI:10.1038/ng1461 PMID:16505173 (ARVD10) 著者 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 タイトル Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. 雑誌 Circulation 113:1171-9 (2006) DOI:10.1161/CIRCULATIONAHA.105.583674 PMID:17033975 (ARVD11) 著者 Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ タイトル Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. 雑誌 Am J Hum Genet 79:978-84 (2006) DOI:10.1086/509122 PMID:17924338 (ARVD12) 著者 Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ タイトル A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. 雑誌 Am J Hum Genet 81:964-73 (2007) DOI:10.1086/521633 PMID:23136403 (ARVD13) 著者 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 タイトル Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy. 雑誌 Eur Heart J 34:201-10 (2013) DOI:10.1093/eurheartj/ehs373 PMID:28280076 (ARVD14) 著者 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 タイトル Identification of Cadherin 2 (CDH2) Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy. 雑誌 Circ Cardiovasc Genet 10:e001605 (2017) DOI:10.1161/CIRCGENETICS.116.001605 |