Details of Disease

Disease Name

Familial dilated cardiomyopathy

hypokinetic dilated cardiomyopathy, familial; dilated cardiomyopathy, familial; idiopathic dilated cardiomyopathy; DCM; hereditary dilated cardiomyopathy

Definition

A a genetic form of heart disease that occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.|Editor note: unsure if GARD is familial form

Disease Hierarchy

DISX608J: Dilated cardiomyopathy

DISBA1TN: Familial cardiomyopathy

DISBHDU9: Familial dilated cardiomyopathy

Disease Identifiers

MONDO ID

MONDO_0016333

MESH ID

C536231

UMLS CUI

C0340427

MedGen ID

90951

Orphanet ID

217607

SNOMED CT ID

52029003

General Information of Disease (ID: DISBHDU9)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 16 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CHRM2	TTYEG6Q	Limited	Genetic Variation	[1]
DMD	TTWLFXU	Limited	Genetic Variation	[2]
SCN5A	TTZOVE0	Limited	Genetic Variation	[3]
TNNT2	TTWAS18	Limited	Genetic Variation	[4]
ABCC9	TTEF5MJ	Strong	GermlineCausalMutation	[5]
CRYAB	TT7RUHB	Strong	GermlineCausalMutation	[6]
LAG3	TTNVXAW	Strong	Biomarker	[7]
MYBPC3	TT9WOBN	Strong	GermlineCausalMutation	[8]
MYH7	TTNIMDP	Strong	Genetic Variation	[4]
PLN	TTMCVJF	Strong	Genetic Variation	[9]
PPIF	TTRFQTB	Strong	Biomarker	[10]
PSEN1	TTZ3S8C	Strong	GermlineCausalMutation	[11]
PSEN2	TTWN3F4	Strong	GermlineCausalMutation	[11]
TNNI3	TTNLDK6	Strong	GermlineCausalMutation	[12]
RAF1	TTAN5W2	Definitive	GermlineCausalMutation	[13]
TNNC1	TT8RDXP	Definitive	GermlineCausalMutation	[14]
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⏷ Show the Full List of 16 DTT(s)

This Disease Is Related to 42 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BAG3	OTVXYUDQ	Limited	Biomarker	[15]
MYBPHL	OTD5YFW2	Limited	Unknown	[16]
MYPN	OTHTOFDU	Limited	GermlineCausalMutation	[17]
RBM20	OTOQZNKS	Limited	Genetic Variation	[18]
SDHA	OTOJ8QFF	Disputed	GermlineCausalMutation	[19]
TAF1A	OTEH7OFT	Disputed	GermlineCausalMutation	[20]
ACTC1	OTJU04B1	Strong	Genetic Variation	[21]
ACTN2	OT9FOLD7	Strong	GermlineCausalMutation	[22]
ANKRD1	OTHJ7JV9	Strong	GermlineCausalMutation	[23]
BCAP31	OTKSACR4	Strong	Biomarker	[24]
CAP2	OTC1WFNO	Strong	GermlineCausalMutation	[25]
CNTN3	OTC1274J	Strong	Biomarker	[26]
CSRP3	OTECBJMV	Strong	GermlineCausalMutation	[27]
DES	OTI09KBW	Strong	Biomarker	[28]
DOLK	OT2HTIAN	Strong	GermlineCausalMutation	[29]
DSG2	OTJPB2TO	Strong	GermlineCausalMutation	[30]
ERBIN	OTNWTUA8	Strong	Genetic Variation	[31]
FHL2	OT0OAYWT	Strong	GermlineCausalMutation	[32]
FKTN	OTQ9GCXL	Strong	GermlineCausalMutation	[33]
GATAD1	OT0UZ3EP	Strong	GermlineCausalMutation	[34]
HAND2	OTCXYW4Y	Strong	Genetic Variation	[35]
KCNJ12	OTYN1E1R	Strong	Genetic Variation	[36]
LAMA1	OTQZMP86	Strong	Biomarker	[37]
LAMA4	OTHI7TA0	Strong	GermlineCausalMutation	[38]
LDB3	OTGQL1AM	Strong	GermlineCausalMutation	[39]
MEOX1	OTJEMT2D	Strong	Altered Expression	[40]
MYEF2	OTSXZ356	Strong	Genetic Variation	[41]
MYH6	OT3YNCH1	Strong	GermlineCausalMutation	[8]
MYL12B	OTXMLQOT	Strong	Genetic Variation	[42]
MYL2	OT78PC0C	Strong	Genetic Variation	[43]
MYLK3	OTC58V2Q	Strong	Genetic Variation	[44]
MYOG	OTPLJKFA	Strong	Biomarker	[41]
NEBL	OT2WH1NC	Strong	Genetic Variation	[45]
PRDM16	OT0BGA27	Strong	GermlineCausalMutation	[46]
TCAP	OTQQMJ94	Strong	GermlineCausalMutation	[47]
TMPO	OTL68EL4	Strong	Genetic Variation	[31]
TRIT1	OTCU9FS5	Strong	Biomarker	[48]
TTN	OT0LZ058	Strong	Genetic Variation	[49]
NEXN	OTKB0B0H	Definitive	GermlineCausalMutation	[50]
PPCS	OT344CQO	Definitive	GermlineCausalMutation	[51]
SGCD	OTRBL3NQ	Definitive	Genetic Variation	[52]
TPM1	OTD73X6R	Definitive	Genetic Variation	[53]
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⏷ Show the Full List of 42 DOT(s)

References

1	Proteomics screen to reveal molecular changes mediated by C722G missense mutation in CHRM2 gene.J Proteomics. 2013 Aug 26;89:39-50. doi: 10.1016/j.jprot.2013.05.027. Epub 2013 Jun 4.
2	Familial dilated cardiomyopathy secondary to dystrophin splice site mutation.J Card Fail. 2010 Mar;16(3):194-9. doi: 10.1016/j.cardfail.2009.11.009.
3	Rapid and effective response of the R222Q SCN5A to quinidine treatment in a patient with Purkinje-related ventricular arrhythmia and familial dilated cardiomyopathy: a case report.BMC Med Genet. 2018 Jun 5;19(1):94. doi: 10.1186/s12881-018-0599-4.
4	Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene.Eur Heart J. 2005 Apr;26(8):794-803. doi: 10.1093/eurheartj/ehi193. Epub 2005 Mar 15.
5	ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nat Genet. 2004 Apr;36(4):382-7. doi: 10.1038/ng1329. Epub 2004 Mar 21.
6	alphaB-crystallin mutation in dilated cardiomyopathies: low prevalence in a consecutive series of 200 unrelated probands.Biochem Biophys Res Commun. 2006 Aug 11;346(4):1115-7. doi: 10.1016/j.bbrc.2006.05.203. Epub 2006 Jun 12.
7	Quality assurance of rifampicin-containing fixed-drug combinations in South Africa: dosing implications.Int J Tuberc Lung Dis. 2018 May 1;22(5):537-543. doi: 10.5588/ijtld.17.0697.
8	Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circ Cardiovasc Genet. 2010 Apr;3(2):155-61. doi: 10.1161/CIRCGENETICS.109.912345. Epub 2010 Mar 9.
9	The R9H phospholamban mutation is associated with highly penetrant dilated cardiomyopathy and sudden death in a spontaneous canine model.Gene. 2019 May 20;697:118-122. doi: 10.1016/j.gene.2019.02.022. Epub 2019 Feb 19.
10	Genomic characterization of the human peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor gene: assessment of its role in familial dilated cardiomyopathy.Hum Genet. 1999 Dec;105(6):582-6. doi: 10.1007/s004399900173.
11	Mutations of presenilin genes in dilated cardiomyopathy and heart failure. Am J Hum Genet. 2006 Dec;79(6):1030-9. doi: 10.1086/509900. Epub 2006 Oct 24.
12	Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy.Circ Res. 2009 Aug 14;105(4):375-82. doi: 10.1161/CIRCRESAHA.109.196055. Epub 2009 Jul 9.
13	RAF1 mutations in childhood-onset dilated cardiomyopathy. Nat Genet. 2014 Jun;46(6):635-639. doi: 10.1038/ng.2963. Epub 2014 Apr 28.
14	Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2004 Nov 16;44(10):2033-40. doi: 10.1016/j.jacc.2004.08.027.
15	Differential expression of circulating miRNAs as a novel tool to assess BAG3-associated familial dilated cardiomyopathy.Biosci Rep. 2019 Mar 15;39(3):BSR20180934. doi: 10.1042/BSR20180934. Print 2019 Mar 29.
16	The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
17	Novel mutations in the sarcomeric protein myopalladin in patients with dilated cardiomyopathy.Eur J Hum Genet. 2013 Mar;21(3):294-300. doi: 10.1038/ejhg.2012.173. Epub 2012 Aug 15.
18	Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization.Sci Rep. 2018 Jun 12;8(1):8970. doi: 10.1038/s41598-018-26624-w.
19	Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Eur J Hum Genet. 2010 Oct;18(10):1160-5. doi: 10.1038/ejhg.2010.83. Epub 2010 Jun 16.
20	Recessive TAF1A mutations reveal ribosomopathy in siblings with end-stage pediatric dilated cardiomyopathy. Hum Mol Genet. 2017 Aug 1;26(15):2874-2881. doi: 10.1093/hmg/ddx169.
21	Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2000 Sep;32(9):1687-94. doi: 10.1006/jmcc.2000.1204.
22	Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death.BMC Med Genet. 2014 Sep 16;15:99. doi: 10.1186/s12881-014-0099-0.
23	Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy. Eur Heart J. 2009 Sep;30(17):2128-36. doi: 10.1093/eurheartj/ehp225. Epub 2009 Jun 12.
24	Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23.Am J Hum Genet. 1997 Oct;61(4):909-17. doi: 10.1086/514896.
25	CAP2 mutation leads to impaired actin dynamics and associates with supraventricular tachycardia and dilated cardiomyopathy. J Med Genet. 2019 Apr;56(4):228-235. doi: 10.1136/jmedgenet-2018-105498. Epub 2018 Dec 5.
26	Health status of cardiac genetic disease patients and their at-risk relatives.Int J Cardiol. 2013 May 25;165(3):448-53. doi: 10.1016/j.ijcard.2011.08.083. Epub 2011 Sep 17.
27	Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Mol Genet Metab. 2003 Sep-Oct;80(1-2):207-15. doi: 10.1016/s1096-7192(03)00142-2.
28	Cardiomyopathy: molecular and immunological aspects (review).Int J Mol Med. 2003 Jan;11(1):13-6.
29	Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation. PLoS Genet. 2011 Dec;7(12):e1002427. doi: 10.1371/journal.pgen.1002427. Epub 2011 Dec 29.
30	A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. Mol Genet Metab. 2008 Sep-Oct;95(1-2):74-80. doi: 10.1016/j.ymgme.2008.06.005. Epub 2008 Aug 3.
31	Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy. Hum Mutat. 2005 Dec;26(6):566-74. doi: 10.1002/humu.20250.
32	Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy. Biochem Biophys Res Commun. 2007 May 25;357(1):162-7. doi: 10.1016/j.bbrc.2007.03.128. Epub 2007 Mar 30.
33	Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. 2006 Nov;60(5):597-602. doi: 10.1002/ana.20973.
34	Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy. Circ Cardiovasc Genet. 2011 Dec;4(6):585-94. doi: 10.1161/CIRCGENETICS.111.961052. Epub 2011 Sep 30.
35	HAND2 loss-of-function mutation causes familial dilated cardiomyopathy. Eur J Med Genet. 2019 Sep;62(9):103540. doi: 10.1016/j.ejmg.2018.09.007. Epub 2018 Sep 12.
36	Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy.Medicine (Baltimore). 2017 Aug;96(33):e7727. doi: 10.1097/MD.0000000000007727.
37	Dual bronchodilation in COPD: lung function and patient-reported outcomes - a review.Int J Chron Obstruct Pulmon Dis. 2016 Dec 30;12:141-168. doi: 10.2147/COPD.S116719. eCollection 2017.
38	Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation. 2007 Jul 31;116(5):515-25. doi: 10.1161/CIRCULATIONAHA.107.689984. Epub 2007 Jul 23.
39	A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C.J Biol Chem. 2004 Feb 20;279(8):6746-52. doi: 10.1074/jbc.M311849200. Epub 2003 Dec 3.
40	Meox1 accelerates myocardial hypertrophic decompensation through Gata4.Cardiovasc Res. 2018 Feb 1;114(2):300-311. doi: 10.1093/cvr/cvx222.
41	Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32.Circulation. 1995 Dec 15;92(12):3387-9. doi: 10.1161/01.cir.92.12.3387.
42	Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy.ESC Heart Fail. 2019 Apr;6(2):406-415. doi: 10.1002/ehf2.12410. Epub 2019 Jan 28.
43	Novel familial dilated cardiomyopathy mutation in MYL2 affects the structure and function of myosin regulatory light chain.FEBS J. 2015 Jun;282(12):2379-93. doi: 10.1111/febs.13286. Epub 2015 Apr 16.
44	Identification of MYLK3 mutations in familial dilated cardiomyopathy.Sci Rep. 2017 Dec 13;7(1):17495. doi: 10.1038/s41598-017-17769-1.
45	Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies.Arch Med Sci. 2016 Apr 1;12(2):263-78. doi: 10.5114/aoms.2016.59250. Epub 2016 Apr 11.
46	Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. Am J Hum Genet. 2013 Jul 11;93(1):67-77. doi: 10.1016/j.ajhg.2013.05.015. Epub 2013 Jun 13.
47	Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.Clin Transl Sci. 2008 May;1(1):21-6. doi: 10.1111/j.1752-8062.2008.00017.x.
48	Imaging findings of inflammatory pseudotumor-like follicular dendritic cell tumors of the liver: Two case reports and literature review.World J Gastroenterol. 2019 Dec 7;25(45):6693-6703. doi: 10.3748/wjg.v25.i45.6693.
49	A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death.Hum Genet. 2019 May;138(5):515-524. doi: 10.1007/s00439-019-01973-2. Epub 2019 Feb 4.
50	Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy. Nat Med. 2009 Nov;15(11):1281-8. doi: 10.1038/nm.2037. Epub 2009 Nov 1.
51	Mutations in PPCS, Encoding Phosphopantothenoylcysteine Synthetase, Cause Autosomal-Recessive Dilated Cardiomyopathy. Am J Hum Genet. 2018 Jun 7;102(6):1018-1030. doi: 10.1016/j.ajhg.2018.03.022. Epub 2018 May 10.
52	Molecular genetics of left ventricular dysfunction.Curr Mol Med. 2001 Mar;1(1):81-90. doi: 10.2174/1566524013364077.
53	The structural basis of alpha-tropomyosin linked (Asp230Asn) familial dilated cardiomyopathy.J Mol Cell Cardiol. 2017 Jul;108:127-137. doi: 10.1016/j.yjmcc.2017.06.001. Epub 2017 Jun 7.