Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM ("familial" DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of "familial" DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an "idiopathic" DCM. Current hypotheses regarding causes of "idiopathic" DCM focus on myocarditis induced by enterovirus and subsequent autoimmune myocardium impairments. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with "idiopathic" DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of the myocardium or cardiac chambers
BC43 Cardiomyopathy
H00294 Dilated cardiomyopathy
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H00294 Dilated cardiomyopathy
Cellular process
nt06539 Cytoskeleton in muscle cells
H00294 Dilated cardiomyopathy
nt06545 Cornified envelope formation
H00294 Dilated cardiomyopathy
Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA
Title
Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.
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.
Carniel E, Taylor MR, Sinagra G, Di Lenarda A, Ku L, Fain PR, Boucek MM, Cavanaugh J, Miocic S, Slavov D, Graw SL, Feiger J, Zhu XZ, Dao D, Ferguson DA, Bristow MR, Mestroni L
Title
Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.
Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Zuchner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE
Title
Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.
Li Y, Ma K, Dong Z, Gao S, Zhang J, Huang S, Yang J, Fang G, Li Y, Li X, Welch C, Griffin EL, Ramaswamy P, Valivullah Z, Liu X, Dong J, Wang DW, Du J, Chung WK, Li Y
Title
Frameshift variants in C10orf71 cause dilated cardiomyopathy in human, mouse, and organoid models.
Ganapathi M, Argyriou L, Martinez-Azorin F, Morlot S, Yigit G, Lee TM, Auber B, von Gise A, Petrey DS, Thiele H, Cyganek L, Sabater-Molina M, Ahimaz P, Cabezas-Herrera J, Sorli-Garcia M, Zibat A, Siegelin MD, Burfeind P, Buchovecky CM, Hasenfuss G, Honig B, Li Y, Iglesias AD, Wollnik B
Title
Bi-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis.
Jones EG, Mazaheri N, Maroofian R, Zamani M, Seifi T, Sedaghat A, Shariati G, Jamshidi Y, Allen HD, Wehrens XHT, Galehdari H, Landstrom AP
Title
Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy.
Hakui H, Kioka H, Miyashita Y, Nishimura S, Matsuoka K, Kato H, Tsukamoto O, Kuramoto Y, Takuwa A, Takahashi Y, Saito S, Ohta K, Asanuma H, Fu HY, Shinomiya H, Yamada N, Ohtani T, Sawa Y, Kitakaze M, Takashima S, Sakata Y, Asano Y
Title
Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated cardiomyopathy requiring heart transplantation.
Verhagen JMA, van den Born M, van der Linde HC, G J Nikkels P, Verdijk RM, Kivlen MH, van Unen LMA, Baas AF, Ter Heide H, van Osch-Gevers L, Hoogeveen-Westerveld M, Herkert JC, Bertoli-Avella AM, van Slegtenhorst MA, Wessels MW, Verheijen FW, Hassel D, Hofstra RMW, Hegde RS, van Hasselt PM, van Ham TJ, van de Laar IMBH
Title
Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy.
Koopmann TT, Jamshidi Y, Naghibi-Sistani M, van der Klift HM, Birjandi H, Al-Hassnan Z, Alwadai A, Zifarelli G, Karimiani EG, Sedighzadeh S, Bahreini A, Nouri N, Peter M, Watanabe K, van Duyvenvoorde HA, Ruivenkamp CAL, Teunissen AKK, Ten Harkel ADJ, van Duinen SG, Haak MC, Prada CE, Santen GWE, Maroofian R
Title
Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy.
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
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of the myocardium or cardiac chambers
BC43 Cardiomyopathy
H00292 Hypertrophic cardiomyopathy
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H00292 Hypertrophic cardiomyopathy
Cellular process
nt06539 Cytoskeleton in muscle cells
H00292 Hypertrophic cardiomyopathy
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.
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.
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.
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
Title
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
Title
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
Title
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
Title
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
Title
Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24.
Olive M, Abdul-Hussein S, Oldfors A, Gonzalez-Costello J, van der Ven PF, Furst DO, Gonzalez L, Moreno D, Torrejon-Escribano B, Alio J, Pou A, Ferrer I, Tajsharghi H
Title
New cardiac and skeletal protein aggregate myopathy associated with combined MuRF1 and MuRF3 mutations.
Myofibrillar myopathy (MFM) is a group of genetically distinct disorders linked by common morphologic features observed on muscle histology. MFM is characterized by slowly progressive weakness that can involve both proximal and distal muscles. Distal muscle weakness is more pronounced than proximal weakness. All disease proteins identified to date are involved in maintaining the structural integrity of the Z-disk. The pathology includes accumulations of these proteins irrespective of primary gene defect, suggesting that these share molecular pathways involved in actin dynamics organized by the Z-disk. Besides accumulations of these proteins, congophilic amyloid products of myofibrillar degradation and ectopic aggregation of dystrophin and gelsolin appear in abnormal myofibers.
Category
Nervous system disease; Musculoskeletal disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Diseases of neuromuscular junction or muscle
Primary disorders of muscles
8C76 Myofibrillar myopathy
H00595 Myofibrillar myopathies
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00595 Myofibrillar myopathies
Hedberg-Oldfors C, Meyer R, Nolte K, Abdul Rahim Y, Lindberg C, Karason K, Thuestad IJ, Visuttijai K, Geijer M, Begemann M, Kraft F, Lausberg E, Hitpass L, Gotzl R, Luna EJ, Lochmuller H, Koschmieder S, Gramlich M, Gess B, Elbracht M, Weis J, Kurth I, Oldfors A, Knopp C
Title
Loss of supervillin causes myopathy with myofibrillar disorganization and autophagic vacuoles.
Weterman MA, Barth PG, van Spaendonck-Zwarts KY, Aronica E, Poll-The BT, Brouwer OF, van Tintelen JP, Qahar Z, Bradley EJ, de Wissel M, Salviati L, Angelini C, van den Heuvel L, Thomasse YE, Backx AP, Nurnberg G, Nurnberg P, Baas F
Title
Recessive MYL2 mutations cause infantile type I muscle fibre disease and cardiomyopathy.
Ghaoui R, Palmio J, Brewer J, Lek M, Needham M, Evila A, Hackman P, Jonson PH, Penttila S, Vihola A, Huovinen S, Lindfors M, Davis RL, Waddell L, Kaur S, Yiannikas C, North K, Clarke N, MacArthur DG, Sue CM, Udd B
Title
Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy.
Left ventricular noncompaction (LVNC) is a rare and potentially progressive cardiomyopathy, characterized by the presence of prominent trabeculations of the left ventricle, associated with progressive systolic failure, stroke and arrhythmia. It has been linked to mutations in several genes, including LIM domain binding protein 3 (ZASP), alpha-dystrobrevin (DTNA), and genes encoding the sarcomeric proteins, beta-myosin heavy chain (MYH7), alpha-cardiac actin (ACTC), and cardiac troponin T (TNNT2).
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of the myocardium or cardiac chambers
BC44 Noncompaction cardiomyopathy
H01216 Left ventricular noncompaction
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06511 NOTCH signaling
H01216 Left ventricular noncompaction
Cellular process
nt06539 Cytoskeleton in muscle cells
H01216 Left ventricular noncompaction
Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA
Title
Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.
Monserrat L, Hermida-Prieto M, Fernandez X, Rodriguez I, Dumont C, Cazon L, Cuesta MG, Gonzalez-Juanatey C, Peteiro J, Alvarez N, Penas-Lado M, Castro-Beiras A
Title
Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects.
