DMD
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.
Reports
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.