Hypertrophic cardiomyopathy

Definition:

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.

References:

[1]. A A Geisterfer-Lowrance, et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990 Sep 7;62(5):999-1006. [Content Brief]

[2]. A J Marian, et al. The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001 Apr;33(4):655-70. [Content Brief]

[3]. A Kimura, et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet. 1997 Aug;16(4):379-82. [Content Brief]

[4]. Ahmet Okay Çağlayan, et al. ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features. Cold Spring Harb Mol Case Stud. 2017 Sep 1;3(5):a001859. [Content Brief]

[5]. Alessandra Ruggiero, et al. Pathogenesis of hypertrophic cardiomyopathy caused by myozenin 2 mutations is independent of calcineurin activity. Cardiovasc Res. 2013 Jan 1;97(1):44-54. [Content Brief]

[6]. Andrew P Landstrom, et al. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. J Mol Cell Cardiol. 2008 Aug;45(2):281-8. [Content Brief]

[7]. Andrew P Landstrom, et al. Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans. J Mol Cell Cardiol. 2007 Jun;42(6):1026-35. [Content Brief]

[8]. Andrew P Landstrom, et al. PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing. Am Heart J. 2011 Jan;161(1):165-71. [Content Brief]

[9]. Christian Geier, et al. Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy. Circulation. 2003 Mar 18;107(10):1390-5. [Content Brief]

[10]. Diane Fatkin, et al. Molecular mechanisms of inherited cardiomyopathies. Physiol Rev. 2002 Oct;82(4):945-80. [Content Brief]

[11]. E Blair, et al. 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. Hum Mol Genet. 2001 May 15;10(11):1215-20. [Content Brief]

[12]. Enkhsaikhan Purevjav, et al. Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations. Hum Mol Genet. 2012 May 1;21(9):2039-53. [Content Brief]

[13]. H Watkins, et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet. 1995 Dec;11(4):434-7. [Content Brief]

[14]. Hideshi Niimura, et al. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation. 2002 Jan 29;105(4):446-51. [Content Brief]

[15]. Hu Wang, et al. Mutations in NEXN, a Z-disc gene, are associated with hypertrophic cardiomyopathy. Am J Hum Genet. 2010 Nov 12;87(5):687-93. [Content Brief]

[16]. J Mogensen, et al. Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J Clin Invest. 1999 May 15;103(10):R39-43. [Content Brief]

[17]. J S Davis, et al. The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation. Cell. 2001 Nov 30;107(5):631-41. [Content Brief]

[18]. Jeanne L Theis, et al. Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006 Dec 29;351(4):896-902. [Content Brief]

[19]. Juan Pablo Ochoa, et al. Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2018 Nov 13;72(20):2457-2467. [Content Brief]

[20]. K Poetter, et al. Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet. 1996 May;13(1):63-9. [Content Brief]

[21]. L Thierfelder, et al. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994 Jun 3;77(5):701-12. [Content Brief]

[22]. M Satoh, et al. Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene. Biochem Biophys Res Commun. 1999 Aug 27;262(2):411-7. [Content Brief]

[23]. Rafael Valdés-Mas, et al. Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy. Nat Commun. 2014 Oct 29;5:5326. [Content Brief]

[24]. Takeharu Hayashi, et al. Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2004 Jan 2;313(1):178-84. [Content Brief]

[25]. Takeharu Hayashi, et al. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. J Am Coll Cardiol. 2004 Dec 7;44(11):2192-201. [Content Brief]

[26]. Vlad C Vasile, et al. A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006 Jul 7;345(3):998-1003. [Content Brief]

[27]. W M Franz, et al. Cardiomyopathies: from genetics to the prospect of treatment. Lancet. 2001 Nov 10;358(9293):1627-37. [Content Brief]

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