KEGG   DISEASE: 肥大型心筋症
エントリ  
H00292                                                             
名称    
肥大型心筋症
概要    
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, myfibrillar 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 myfilament 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.
カテゴリ  
心臓病
階層分類  
ヒト疾患 [BR:jp08402]
 循環器系疾患
  心疾患
   H00292  肥大型心筋症
ICD-11 による疾患分類 [BR:jp08403]
 11 循環器系の疾患
  心筋または心室の疾患
   BC43  心筋症
    H00292  肥大型心筋症
特定疾患 (難病) [jp08407.html]
 H00292
パスウェイ 
hsa05410  肥大型心筋症
関連パスウェイ
hsa04260  Cardiac muscle contraction
hsa04261  Adrenergic signaling in cardiomyocytes
病因遺伝子 
(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]
(CMH17) JPH2 [HSA:57158] [KO:K19530]
(CMH18) PLN [HSA:5350] [KO:K05852]
(CMH20) NEXN [HSA:91624] [KO:K23918]
(CMH22) MYPN [HSA:84665] [KO:K22028]
(CMH23) ACTN2 [HSA:88] [KO:K21073]
(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) FMNL3 [HSA:91010] [KO:K23957]
環境要因  
Athletic training
治療薬   
アミオダロン塩酸塩 [DR:D00636]
リンク   
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 607487 617047 618052 619402 615248 612158 601493
文献    
  著者
Fatkin D, Graham RM
  タイトル
Molecular mechanisms of inherited cardiomyopathies.
  雑誌
Physiol Rev 82:945-80 (2002)
DOI:10.1152/physrev.00012.2002
文献    
  著者
Moolman-Smook JC, Mayosi BM, Brink PA, Corfield VA
  タイトル
Molecular genetics of cardiomyopathy: changing times, shifting paradigms.
  雑誌
Cardiovasc J S Afr 14:145-55 (2003)
文献    
  著者
Franz WM, Muller OJ, Katus HA
  タイトル
Cardiomyopathies: from genetics to the prospect of treatment.
  雑誌
Lancet 358:1627-37 (2001)
DOI:10.1016/S0140-6736(01)06657-0
文献    
  著者
Marian AJ, Roberts R
  タイトル
The molecular genetic basis for hypertrophic cardiomyopathy.
  雑誌
J Mol Cell Cardiol 33:655-70 (2001)
DOI:10.1006/jmcc.2001.1340
文献    
PMID:1975517 (MYH7)
  著者
Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG
  タイトル
A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation.
  雑誌
Cell 62:999-1006 (1990)
DOI:10.1016/0092-8674(90)90274-i
文献    
PMID:11733062 (MYLK2)
  著者
Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, Epstein ND
  タイトル
The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation.
  雑誌
Cell 107:631-41 (2001)
DOI:10.1016/s0092-8674(01)00586-4
文献    
PMID:14672715 (CAV3)
  著者
Hayashi T, Arimura T, Ueda K, Shibata H, Hohda S, Takahashi M, Hori H, Koga Y, Oka N, Imaizumi T, Yasunami M, Kimura A
  タイトル
Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy.
  雑誌
Biochem Biophys Res Commun 313:178-84 (2004)
DOI:10.1016/j.bbrc.2003.11.101
文献    
PMID:8205619 (TNNT2 TPM1)
  著者
Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE
  タイトル
Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.
  雑誌
Cell 77:701-12 (1994)
DOI:10.1016/0092-8674(94)90054-x
文献    
PMID:7493025 (MYBPC3)
  著者
Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE
  タイトル
Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy.
  雑誌
Nat Genet 11:434-7 (1995)
DOI:10.1038/ng1295-434
文献    
PMID:11371514 (PRKAG2)
  著者
Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H
  タイトル
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.
  雑誌
Hum Mol Genet 10:1215-20 (2001)
DOI:10.1093/hmg/10.11.1215
文献    
PMID:9241277 (TNNI3)
  著者
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
  タイトル
Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.
  雑誌
Nat Genet 16:379-82 (1997)
DOI:10.1038/ng0897-379
文献    
PMID:8673105 (MYL3 MYL2)
  著者
Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND
  タイトル
Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle.
  雑誌
Nat Genet 13:63-9 (1996)
DOI:10.1038/ng0596-63
文献    
PMID:10462489 (TTN)
  著者
Satoh M, Takahashi M, Sakamoto T, Hiroe M, Marumo F, Kimura A
  タイトル
Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene.
  雑誌
Biochem Biophys Res Commun 262:411-7 (1999)
DOI:10.1006/bbrc.1999.1221
文献    
PMID:10330430 (ACTC1)
  著者
Mogensen J, Klausen IC, Pedersen AK, Egeblad H, Bross P, Kruse TA, Gregersen N, Hansen PS, Baandrup U, Borglum AD
  タイトル
Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.
  雑誌
J Clin Invest 103:R39-43 (1999)
DOI:10.1172/JCI6460
文献    
PMID:12642359 (CSRP3)
  著者
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
  タイトル
Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy.
  雑誌
Circulation 107:1390-5 (2003)
DOI:10.1161/01.cir.0000056522.82563.5f
文献    
PMID:18572189 (TNNC1)
  著者
Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ
  タイトル
Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C.
  雑誌
J Mol Cell Cardiol 45:281-8 (2008)
DOI:10.1016/j.yjmcc.2008.05.003
文献    
PMID:11815426 (MYH6)
  著者
Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE
  タイトル
Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly.
  雑誌
Circulation 105:446-51 (2002)
DOI:10.1161/hc0402.102990
文献    
PMID:16712796 (VCL)
  著者
Vasile VC, Ommen SR, Edwards WD, Ackerman MJ
  タイトル
A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy.
  雑誌
Biochem Biophys Res Commun 345:998-1003 (2006)
DOI:10.1016/j.bbrc.2006.04.151
文献    
PMID:22987565 (MYOZ2)
  著者
Ruggiero A, Chen SN, Lombardi R, Rodriguez G, Marian AJ
  タイトル
Pathogenesis of hypertrophic cardiomyopathy caused by myozenin 2 mutations is independent of calcineurin activity.
  雑誌
Cardiovasc Res 97:44-54 (2013)
DOI:10.1093/cvr/cvs294
文献    
PMID:17509612 (JPH2)
  著者
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
  タイトル
Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans.
  雑誌
J Mol Cell Cardiol 42:1026-35 (2007)
DOI:10.1016/j.yjmcc.2007.04.006
文献    
PMID:21167350 (PLN)
  著者
Landstrom AP, Adekola BA, Bos JM, Ommen SR, Ackerman MJ
  タイトル
PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.
  雑誌
Am Heart J 161:165-71 (2011)
DOI:10.1016/j.ahj.2010.08.001
文献    
PMID:20970104 (NEXN)
  著者
Wang H, Li Z, Wang J, Sun K, Cui Q, Song L, Zou Y, Wang X, Liu X, Hui R, Fan Y
  タイトル
Mutations in NEXN, a Z-disc gene, are associated with hypertrophic cardiomyopathy.
  雑誌
Am J Hum Genet 87:687-93 (2010)
DOI:10.1016/j.ajhg.2010.10.002
文献    
PMID:22286171 (MYPN)
  著者
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
  タイトル
Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations.
  雑誌
Hum Mol Genet 21:2039-53 (2012)
DOI:10.1093/hmg/dds022
文献    
PMID:17097056 (ACTN2 LDB3)
  著者
Theis JL, Bos JM, Bartleson VB, Will ML, Binder J, Vatta M, Towbin JA, Gersh BJ, Ommen SR, Ackerman MJ
  タイトル
Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy.
  雑誌
Biochem Biophys Res Commun 351:896-902 (2006)
DOI:10.1016/j.bbrc.2006.10.119
文献    
PMID:15582318 (TCAP)
  著者
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
  タイトル
Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
  雑誌
J Am Coll Cardiol 44:2192-201 (2004)
DOI:10.1016/j.jacc.2004.08.058
文献    
PMID:25351925 (FLNC)
  著者
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
  タイトル
Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy.
  雑誌
Nat Commun 5:5326 (2014)
DOI:10.1038/ncomms6326
文献    
PMID:28630369 (ALPK3)
  著者
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
  タイトル
ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features.
  雑誌
Cold Spring Harb Mol Case Stud 3:a001859 (2017)
DOI:10.1101/mcs.a001859
文献    
PMID:30442288 (FMNL3)
  著者
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
  タイトル
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy.
  雑誌
J Am Coll Cardiol 72:2457-2467 (2018)
DOI:10.1016/j.jacc.2018.10.001
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