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.
Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H
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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.
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
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Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.
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
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Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy.
PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.
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
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Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations.
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
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Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
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
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Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy.
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
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Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy.
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
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Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24.
