| H00292 | |
| H number | H00292 |
| Name | Hypertrophic cardiomyopathy |
| Description | Hypertrophic cardiomyopathy (HCM/CMH) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in the genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction. |
| Category | Cardiovascular disease DIS_PATHWAY hsa05410 Hypertrophic cardiomyopathy |
| Network | nt06528(H00292) Calcium signaling |
| Gene | (CMH1) MYH7 [HSA:4625] [KO:K17751] (CMH1) MYLK2 [HSA:85366] [KO:K00907] (CMH1) CAV3 [HSA:859] [KO:K12959] (CMH2) TNNT2 [HSA:7139] [KO:K12045] (CMH3) TPM1 [HSA:7168] [KO:K10373] (CMH4) MYBPC3 [HSA:4607] [KO:K12568] (CMH6) PRKAG2 [HSA:51422] [KO:K07200] (CMH7) TNNI3 [HSA:7137] [KO:K12044] (CMH8) MYL3 [HSA:4634] [KO:K12749] (CMH9) TTN [HSA:7273] [KO:K12567] (CMH10) MYL2 [HSA:4633] [KO:K10351] (CMH11) ACTC1 [HSA:70] [KO:K12314] (CMH12) CSRP3 [HSA:8048] [KO:K09377] (CMH13) TNNC1 [HSA:7134] [KO:K05865] (CMH14) MYH6 [HSA:4624] [KO:K17751] (CMH15) VCL [HSA:7414] [KO:K05700] (CMH16) MYOZ2 [HSA:51778] [KO:K26050] (CMH17) JPH2 [HSA:57158] [KO:K19530] (CMH18) PLN [HSA:5350] [KO:K05852] (CMH20) NEXN [HSA:91624] [KO:K23918] (CMD1KK/CMH22) MYPN [HSA:84665] [KO:K22028] (CMD1AA/CMH23) ACTN2 [HSA:88] [KO:K21073] (CMD1C/CMH24) LDB3 [HSA:11155] [KO:K19867] (CMH25) TCAP [HSA:8557] [KO:K19879] (CMH26) FLNC [HSA:2318] [KO:K04437] (CMH27) ALPK3 [HSA:57538] [KO:K08868] (CMH28) FHOD3 [HSA:80206] [KO:K23939] (CMH29) KLHL24 [HSA:54800] [KO:K10461] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Mavacamten [DR:D12265] |
| Comment | - |
| Other DBs | ICD-11: BC43.1 ICD-10: I42 OMIM: 192600 115195 115196 115197 600858 613690 608751 613765 608758 612098 612124 613243 613251 613255 613838 613873 613874 613876 615248 612158 601493 607487 617047 618052 619402 620236 |
| Reference | PMID:12270949 AUTHORS Fatkin D, Graham RM TITLE Molecular mechanisms of inherited cardiomyopathies. JOURNAL Physiol Rev 82:945-80 (2002) DOI:10.1152/physrev.00012.2002 PMID:12844200 AUTHORS Moolman-Smook JC, Mayosi BM, Brink PA, Corfield VA TITLE Molecular genetics of cardiomyopathy: changing times, shifting paradigms. JOURNAL Cardiovasc J S Afr 14:145-55 (2003) PMID:11716909 AUTHORS Franz WM, Muller OJ, Katus HA TITLE Cardiomyopathies: from genetics to the prospect of treatment. JOURNAL Lancet 358:1627-37 (2001) DOI:10.1016/S0140-6736(01)06657-0 PMID:11273720 AUTHORS Marian AJ, Roberts R TITLE The molecular genetic basis for hypertrophic cardiomyopathy. JOURNAL J Mol Cell Cardiol 33:655-70 (2001) DOI:10.1006/jmcc.2001.1340 PMID:1975517 (MYH7) AUTHORS Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG TITLE A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. JOURNAL Cell 62:999-1006 (1990) DOI:10.1016/0092-8674(90)90274-i PMID:11733062 (MYLK2) AUTHORS Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, Epstein ND TITLE The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation. JOURNAL Cell 107:631-41 (2001) DOI:10.1016/s0092-8674(01)00586-4 PMID:14672715 (CAV3) AUTHORS Hayashi T, Arimura T, Ueda K, Shibata H, Hohda S, Takahashi M, Hori H, Koga Y, Oka N, Imaizumi T, Yasunami M, Kimura A TITLE Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. JOURNAL Biochem Biophys Res Commun 313:178-84 (2004) DOI:10.1016/j.bbrc.2003.11.101 PMID:8205619 (TNNT2 TPM1) AUTHORS Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE TITLE Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. JOURNAL Cell 77:701-12 (1994) DOI:10.1016/0092-8674(94)90054-x PMID:7493025 (MYBPC3) AUTHORS Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE TITLE Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. JOURNAL Nat Genet 11:434-7 (1995) DOI:10.1038/ng1295-434 PMID:11371514 (PRKAG2) AUTHORS Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H TITLE Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. JOURNAL Hum Mol Genet 10:1215-20 (2001) DOI:10.1093/hmg/10.11.1215 PMID:9241277 (TNNI3) AUTHORS Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T TITLE Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. JOURNAL Nat Genet 16:379-82 (1997) DOI:10.1038/ng0897-379 PMID:8673105 (MYL3 MYL2) AUTHORS Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND TITLE Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. JOURNAL Nat Genet 13:63-9 (1996) DOI:10.1038/ng0596-63 PMID:10462489 (TTN) AUTHORS Satoh M, Takahashi M, Sakamoto T, Hiroe M, Marumo F, Kimura A TITLE Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene. JOURNAL Biochem Biophys Res Commun 262:411-7 (1999) DOI:10.1006/bbrc.1999.1221 PMID:10330430 (ACTC1) AUTHORS Mogensen J, Klausen IC, Pedersen AK, Egeblad H, Bross P, Kruse TA, Gregersen N, Hansen PS, Baandrup U, Borglum AD TITLE Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. JOURNAL J Clin Invest 103:R39-43 (1999) DOI:10.1172/JCI6460 PMID:12642359 (CSRP3) AUTHORS Geier C, Perrot A, Ozcelik C, Binner P, Counsell D, Hoffmann K, Pilz B, Martiniak Y, Gehmlich K, van der Ven PF, Furst DO, Vornwald A, von Hodenberg E, Nurnberg P, Scheffold T, Dietz R, Osterziel KJ TITLE Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy. JOURNAL Circulation 107:1390-5 (2003) DOI:10.1161/01.cir.0000056522.82563.5f PMID:18572189 (TNNC1) AUTHORS Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ TITLE Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. JOURNAL J Mol Cell Cardiol 45:281-8 (2008) DOI:10.1016/j.yjmcc.2008.05.003 PMID:11815426 (MYH6) AUTHORS Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE TITLE Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. JOURNAL Circulation 105:446-51 (2002) DOI:10.1161/hc0402.102990 PMID:16712796 (VCL) AUTHORS Vasile VC, Ommen SR, Edwards WD, Ackerman MJ TITLE A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. JOURNAL Biochem Biophys Res Commun 345:998-1003 (2006) DOI:10.1016/j.bbrc.2006.04.151 PMID:22987565 (MYOZ2) AUTHORS Ruggiero A, Chen SN, Lombardi R, Rodriguez G, Marian AJ TITLE Pathogenesis of hypertrophic cardiomyopathy caused by myozenin 2 mutations is independent of calcineurin activity. JOURNAL Cardiovasc Res 97:44-54 (2013) DOI:10.1093/cvr/cvs294 PMID:17509612 (JPH2) AUTHORS Landstrom AP, Weisleder N, Batalden KB, Bos JM, Tester DJ, Ommen SR, Wehrens XH, Claycomb WC, Ko JK, Hwang M, Pan Z, Ma J, Ackerman MJ TITLE Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans. JOURNAL J Mol Cell Cardiol 42:1026-35 (2007) DOI:10.1016/j.yjmcc.2007.04.006 PMID:21167350 (PLN) AUTHORS Landstrom AP, Adekola BA, Bos JM, Ommen SR, Ackerman MJ TITLE PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing. JOURNAL Am Heart J 161:165-71 (2011) DOI:10.1016/j.ahj.2010.08.001 PMID:20970104 (NEXN) AUTHORS Wang H, Li Z, Wang J, Sun K, Cui Q, Song L, Zou Y, Wang X, Liu X, Hui R, Fan Y TITLE Mutations in NEXN, a Z-disc gene, are associated with hypertrophic cardiomyopathy. JOURNAL Am J Hum Genet 87:687-93 (2010) DOI:10.1016/j.ajhg.2010.10.002 PMID:22286171 (MYPN) AUTHORS Purevjav E, Arimura T, Augustin S, Huby AC, Takagi K, Nunoda S, Kearney DL, Taylor MD, Terasaki F, Bos JM, Ommen SR, Shibata H, Takahashi M, Itoh-Satoh M, McKenna WJ, Murphy RT, Labeit S, Yamanaka Y, Machida N, Park JE, Alexander PM, Weintraub RG, Kitaura Y, Ackerman MJ, Kimura A, Towbin JA TITLE Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations. JOURNAL Hum Mol Genet 21:2039-53 (2012) DOI:10.1093/hmg/dds022 PMID:17097056 (ACTN2 LDB3) AUTHORS Theis JL, Bos JM, Bartleson VB, Will ML, Binder J, Vatta M, Towbin JA, Gersh BJ, Ommen SR, Ackerman MJ TITLE Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy. JOURNAL Biochem Biophys Res Commun 351:896-902 (2006) DOI:10.1016/j.bbrc.2006.10.119 PMID:15582318 (TCAP) AUTHORS Hayashi T, Arimura T, Itoh-Satoh M, Ueda K, Hohda S, Inagaki N, Takahashi M, Hori H, Yasunami M, Nishi H, Koga Y, Nakamura H, Matsuzaki M, Choi BY, Bae SW, You CW, Han KH, Park JE, Knoll R, Hoshijima M, Chien KR, Kimura A TITLE Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. JOURNAL J Am Coll Cardiol 44:2192-201 (2004) DOI:10.1016/j.jacc.2004.08.058 PMID:25351925 (FLNC) AUTHORS Valdes-Mas R, Gutierrez-Fernandez A, Gomez J, Coto E, Astudillo A, Puente DA, Reguero JR, Alvarez V, Moris C, Leon D, Martin M, Puente XS, Lopez-Otin C TITLE Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy. JOURNAL Nat Commun 5:5326 (2014) DOI:10.1038/ncomms6326 PMID:28630369 (ALPK3) AUTHORS Caglayan AO, Sezer RG, Kaymakcalan H, Ulgen E, Yavuz T, Baranoski JF, Bozaykut A, Harmanci AS, Yalcin Y, Youngblood MW, Yasuno K, Bilguvar K, Gunel M TITLE ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features. JOURNAL Cold Spring Harb Mol Case Stud 3:a001859 (2017) DOI:10.1101/mcs.a001859 PMID:30442288 (FHOD3) AUTHORS Ochoa JP, Sabater-Molina M, Garcia-Pinilla JM, Mogensen J, Restrepo-Cordoba A, Palomino-Doza J, Villacorta E, Martinez-Moreno M, Ramos-Maqueda J, Zorio E, Pena-Pena ML, Garcia-Granja PE, Rodriguez-Palomares JF, Cardenas-Reyes IJ, de la Torre-Carpente MM, Bautista-Paves A, Akhtar MM, Cicerchia MN, Bilbao-Quesada R, Mogollon-Jimenez MV, Salazar-Mendiguchia J, Mesa Latorre JM, Arnaez B, Olavarri-Miguel I, Fuentes-Canamero ME, Lamounier A Jr, Perez Ruiz JM, Climent-Paya V, Perez-Sanchez I, Trujillo-Quintero JP, Lopes LR, Reparaz-Andrade A, Marin-Iglesias R, Rodriguez-Vilela A, Sandin-Fuentes M, Garrote JA, Cortel-Fuster A, Lopez-Garrido M, Fontalba-Romero A, Ripoll-Vera T, Llano-Rivas I, Fernandez-Fernandez X, Isidoro-Garcia M, Garcia-Giustiniani D, Barriales-Villa R, Ortiz-Genga M, Garcia-Pavia P, Elliott PM, Gimeno JR, Monserrat L TITLE Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy. JOURNAL J Am Coll Cardiol 72:2457-2467 (2018) DOI:10.1016/j.jacc.2018.10.001 PMID:30715372 (KLHL24) AUTHORS Hedberg-Oldfors C, Abramsson A, Osborn DPS, Danielsson O, Fazlinezhad A, Nilipour Y, Hubbert L, Nennesmo I, Visuttijai K, Bharj J, Petropoulou E, Shoreim A, Vona B, Ahangari N, Lopez MD, Doosti M, Banote RK, Maroofian R, Edling M, Taherpour M, Zetterberg H, Karimiani EG, Oldfors A, Jamshidi Y TITLE Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24. JOURNAL Hum Mol Genet 28:1919-1929 (2019) DOI:10.1093/hmg/ddz032 |