Gene discovery reference:

Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000; 343:1688-1696.

Other MYH7 reports:

Villard E, Duboscq-Bidot L, Charron P, Benaiche A, Conraads V, Sylvius N, Komajda M. Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene. Eur Heart J. 2005;Apr;26(8):794-803. Epub 2005 Mar 15.



Gene discovery reference:

Olson TM, Michels VV, Thibodeau SN, Tai YS, and Keating MT. Cardiac Actin. ACTC (cardiac actin) is an essential component of the cardiac sarcomere. Science. 1998; 280:750-752.

Actin mutation frequency in FDC/IDC:

Olson et al., 1998: 2/???

Mayosi 1999: 0/8 FDC; 0/46 IDC

Takai 1999: 0/30 FDC; 0/106 IDC

Tesson 2000: 0/43 IDC & 0/43 FDC

Mohapatra 2003: 0/110 IDC


Mutation Frequency References:

Mayosi B, Khogali S, Zhang B, and Watkins H.  Cardiac and skeletal actin gene mutations are not a common cause of dilated cardiomyopathy. J Med Genet. 1999;36:796-797.

Takai E, Akita H, Shiga N, Kanazawa K, Yamada S, Terashima M, Matsuda Y, Iwai C, Kawai K, Yokota Y, and Yokoyama M.  Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy. Am J Med Genet. 1999 Oct 8;86(4):325-7

Tesson F, Sylvius N, Pilotto A, Dubosq-Bidot L, Peuchmaurd M, Bouchier C, Benaiche A, Mangin L, Charron P, Gavazzi A, Tavazzi L, Arbustini E, Komajda M. Epidemiology of desmin and cardiac actin gene mutations in a European population of dilated cardiomyopathy. Eur Heart J. 2000;21:1872-6.

Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG, Chrisco MA, Murphy RT, Lurie PR, Schwartz RJ, Elliott PM, Vatta M, McKenna W, Towbin JA, Bowles NE. Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Mol Genet Metab. 2003;80:207-15.



The very large protein dystrophin, a product of the DMD gene which resides on the X chromosome, is the major protein of the dystrophin-associated glycoprotein complex that is essential to transduce the force of contraction to the cell membrane and the extracellular complex. The DMD gene was identified as the cause of Duchenne’s and Becker’s muscular dystrophy in 1987 in Lou Kunkel’s lab, one of the first successes in reverse genetics.

X-linked FDC probably accounts for approximately 5-10% of FDC, and the most common known causation for X-linked FDC results from mutations in the dystrophin gene identified in several families displaying X-linked inheritance. These references are provided below. In some cases, DCM has also been noted to be the only or presenting feature in individuals who have Becker muscular dystrophy or in female carriers. Dystrophin mutations have also been identified in male patients diagnosed with IDC, suggesting that this may be a rare cause of sporadic cases.

Several of the key reports have been provided below if the reader wishes to pursue additional details of dystrophin-associated cardiomyopathy.


Title. Brief report:  Deletion of the dystrophin muscle-promoter region associated with x-linked dilated cardiomyopathy.

Authors. Muntoni F, Cau M, Ganau A, Congiu R, Arvedi G, Mateddu A, Marrosu MG, Cianchetti C, Realdi G, Cao A, Melis MA.

Journal. N Engl J Med 1993:329:921-925.

PMID: 8361506

Title. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus.

Authors. Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, McCabe ER, Swift M.

Journal. Circulation 1993:87:1854-65.

PMID: 0008504498

Title. A point mutation in the 5′ splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy.

Authors. Milasin J, Muntoni F, Severini GM, Bartoloni L, Vatta M, Krajinovic M, Mateddu A, Angelini C, Camerini F, Falaschi A, Mestroni L, Giacca M.

Journal. Hum Mol Genet 1996:5:73-9.

PMID: 8789442

Title. A 5′ dystrophin duplication mutation causes membrane deficiency of alpha-dystroglycan in a family with X-linked cardiomyopathy.

Authors. Bies R, Maeda M, Roberds S, Holder E, Bohlmeyer T, Young J, Campbell K.

Journal. J Mol Cell Cardiol 1997:29:3175-3188.

PMID: 9441825

Title. Dystrophin gene abnormalities in two patients with idiopathic dilated cardiomyopathy.

Authors. Muntoni F, Di Lenarda A, Porcu M, Sinagra G, Mateddu A, Marrosu G, Ferlini A, Cau M, Milasin J, Melis MA, Marrosu MG, Cianchetti C, Sanna A, Falaschi A, Camerini F, Giacca M, Mestroni L.

Journal. Heart 1997:78:608-12.

PMID: 9470882

Title. Evidence for a dystrophin missense mutation as a cause of X-linked dilated cardiomyopathy.

Authors. Ortiz-Lopez R, Li H, Su J, Goythia V, Towbin J.

Journal. Circ 1997:95:2434-2440.

PMID: 9170407

Title. A novel Alu-like element rearranged in the dystrophin gene causes a splicing mutation in a family with X-linked dilated cardiomyopathy.

Authors. Ferlini A, Galie N, Merlini L, Sewry C, Branzi A, Muntoni F.

Journal. Am J Hum Genet 1998:63:436-446.

PMID: 9683584

Title. Insertional mutation by transposable element, L1, in the DMD gene results in X-linked dilated cardiomyopathy.

Authors. Yoshida K, Nakamura A, Yazaki M, Ikeda S, Takeda S.

Journal. Hum Mol Genet 1998:7:1129-1132.

PMID: 9618170

Title. Association of nonsense mutation of dystrophin gene with disruption of sarcoglycan complex in X-linked dilated cardiomyopathy.

Authors. Franz WM, Muller M, Muller OJ, Herrmann R, Rothmann T, Cremer M, Cohn RD, Voit T, Katus HA.

Journal. Lancet 2000:355:1781-5.

PMID: 10832829

Title. Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies.

Authors. Politano L, Nigro V, Nigro G, Petretta V, Passamano L, Papparella S, DiSomma S, Comi L.

Journal. J Am Med Assoc 1996:275:1335-1338.

PMID: 8614119

Title. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study.

Authors. Hoogerwaard EM, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Leschot NJ, Van Essen AJ, Brunner HG, van der Wouw PA, Wilde A, Ade Visser M.

Journal. Lancet 1999:353:2116-9.

PMID: 10382696

Title. Dystrophin gene abnormalities in two patients with idiopathic dilated cardiomyopathy.

Authors. Muntoni F, DiLenarda A, Porcu M, Sinagra G, Mateddu A, Marrosu G, Ferlini A, Cau M, Milasin J, Melis M, Marrosu M, Cianchetti C, Sanna A, Falaschi A, Camerini F, Giacca M, Mestroni, L.

Journal. Heart 1997:78:608-612.

PMID: 9470882

Title. Familial dilated cardiomyopathy: from clinical presentation to molecular genetics.

Authors. Arbustini E, Morbini P, Pilotto A, Gavazzi ATavazzi L.

Journal. Eur Heart J 2000:21:1825-32.

PMID: 11052854


Title. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.

Authors. 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.

Journal. J Am Coll Cardiol. 2004 Dec 7;44(11):2192-201.

Department of Molecular Pathogenesis, Medical Research Institute, and Laboratory of Genome Diversity, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 15582318

Citation type: phenotype/genotype (clinical and genetic data).

Study design: candidate gene survey of patients with hypertrophic and dilated cardiomyopathy for TCAP mutations.

Study Summary: The Z-disk component Tcap, which associates into a titin/Tcap/MLP complex, was evaluated for sequence variation in 346 patients with hypertrophic cardiomyopathy and in 136 patients with dilated cardiomyopathy, of which 34 were familial and 102 were sporadic cases. One mutation was identified in a patient with DCM who had presented with heart failure at age 34 and underwent heart transplantation at age 35. The patient’s sister had died of SCD and heart failure at age 26, but DNA was not available for analysis. The patient’s father carried the TCAP mutation but did not have clinical disease. The patient’s mother and maternal uncle had hypertrophic cardiomyopathy, did not carry the TCAP mutation, but did carry a mutation in the gene for myosin protein binding C (MYBPC3). Two TCAP mutations were found in two families with hypertrophic cardiomyopathy. Additional

Comment: The modest clinical genetic data to support a disease-associated DCM phenotype was buttressed by two functional assays to suggest the identified mutation interferes with TCAP’s interaction with MLP, titin and calsarcin-1.


Gene Discovery Report:

Bione S, D’Adamo P, Maestrini E, Gedeon A, Bolhuis P, Toniolo D. A novel X-linked gene, G4.5, is responsible for Barth syndrome. Nat Genet. 1996;12:385-389.

Other TAZ Reports:

Bleyl SB, Mumford BR, Thompson V, Carey JC, Pysher TJ, Chin TK, Ward K. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet. 1997;61:868-72.

D’Adamo P, Fassone L, Gedeon A, Janssen EA, Bione S, Bolhuis PA, Barth PG, Wilson M, Haan E, Orstavik KH, Patton MA, Green AJ, Zammarchi E, Donati MA, Toniolo D. The x-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. Am J Hum Genet. 1997;61:862-867