KEGG   DISEASE: H00292Help
Entry
H00292                      Disease                                

Name
Hypertrophic cardiomyopathy (HCM)
Description
Hypertrophic cardiomyopathy (HCM) 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.
Category
Cardiovascular disease
BRITE hierarchy
Pathway
Hypertrophic cardiomyopathy (HCM)
Gene
MYH7 (mutation) [HSA:4625] [KO:K17751]
TNNT2 (mutation) [HSA:7139] [KO:K12045]
MYBPC3 (mutation) [HSA:4607] [KO:K12568]
TPM1 (mutation) [HSA:7168] [KO:K10373]
TNNI3 (mutation) [HSA:7137] [KO:K12044]
MYL2 (mutation) [HSA:4633] [KO:K10351]
MYL3 (mutation) [HSA:4634] [KO:K12749]
ACTC1 (mutation) [HSA:70] [KO:K12314]
TTN (mutation) [HSA:7273] [KO:K12567]
MYH6 (mutation) [HSA:4624] [KO:K17751]
PRKAG2 (mutation) [HSA:51422] [KO:K07200]
CSRP3 (mutation) [HSA:8048] [KO:K09377]
TNNC1 (mutation) [HSA:7134] [KO:K05865]
VCL (mutation) [HSA:7414] [KO:K05700]
Env factor
Athletic training
Drug
Beta-blockers
Disopyramide [DG:DG00194]
Verapamil [DG:DG00329]
Diltiazem [DG00331]
Other DBs
Reference
PMID:12270949 (gene)
  Authors
Fatkin D, Graham RM
  Title
Molecular mechanisms of inherited cardiomyopathies.
  Journal
Physiol Rev 82:945-80 (2002)
Reference
PMID:12844200 (gene)
  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)
Reference
PMID:11716909 (gene)
  Authors
Franz WM, Muller OJ, Katus HA
  Title
Cardiomyopathies: from genetics to the prospect of treatment.
  Journal
Lancet 358:1627-37 (2001)
Reference
PMID:11273720 (gene)
  Authors
Marian AJ, Roberts R
  Title
The molecular genetic basis for hypertrophic cardiomyopathy.
  Journal
J Mol Cell Cardiol 33:655-70 (2001)
Reference
PMID:18572189 (gene)
  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)
Reference
PMID:16712796 (gene)
  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)
Reference
PMID:15183628 (env_factor ,drug)
  Authors
Elliott P, McKenna WJ
  Title
Hypertrophic cardiomyopathy.
  Journal
Lancet 363:1881-91 (2004)
Reference
PMID:18930982 (drug)
  Authors
Soor GS, Luk A, Ahn E, Abraham JR, Woo A, Ralph-Edwards A, Butany J
  Title
Hypertrophic cardiomyopathy: current understanding and treatment objectives.
  Journal
J Clin Pathol 62:226-35 (2009)
Reference
PMID:19568388 (drug)
  Authors
Marian AJ
  Title
Contemporary treatment of hypertrophic cardiomyopathy.
  Journal
Tex Heart Inst J 36:194-204 (2009)
Reference
PMID:15123994 (drug)
  Authors
Ommen SR, Nishimura RA
  Title
Hypertrophic cardiomyopathy.
  Journal
Curr Probl Cardiol 29:239-91 (2004)

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