Mutations in the human δ-sarcoglycan gene in familial and sporadic dilated cardiomyopathy

Department of Pediatrics, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Journal of Clinical Investigation (Impact Factor: 13.77). 10/2000; 106(5):655-62. DOI: 10.1172/JCI9224
Source: PubMed

ABSTRACT Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), whereas three other genes (actin, lamin A/C, and desmin) cause autosomal dominant DCM; seven other loci for autosomal dominant DCM have been mapped but the genes have not been identified. Hypothesizing that DCM is a disease of the cytoskeleton and sarcolemma, we have focused on candidate genes whose products are found in these structures. Here we report the screening of the human delta-sarcoglycan gene, a member of the dystrophin-associated protein complex, by single-stranded DNA conformation polymorphism analysis and by DNA sequencing in patients with DCM. Mutations affecting the secondary structure were identified in one family and two sporadic cases, whereas immunofluorescence analysis of myocardium from one of these patients demonstrated significant reduction in delta-sarcoglycan staining. No skeletal muscle disease occurred in any of these patients. These data suggest that delta-sarcoglycan is a disease-causing gene responsible for familial and idiopathic DCM and lend support to our "final common pathway" hypothesis that DCM is a cytoskeletalopathy.

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Available from: Jeffrey A Towbin, Mar 12, 2014
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    • "d-Sarcoglycan, another component of the dystrophin-glycoprotein complex, is mutated and reduced in patients that present with DCM. Thus, loss and mutations of d-sarcoglycan may be specifically associated with cardiac rather skeletal myopathies (Tsubata et al., 2000). In support of this, mice deficient for d-but not a-sarcoglycan developed cardiomyopathy, necrosis, and fibrosis with increased mortality around 6 months of age (Coral-Vazquez et al., 1999). "
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    • "Several forms of muscular dystrophy are caused by primary mutations in the genes encoding components of the DAPC [Monaco, 1989; Tsubata et al., 2000]. Primary mutations in the dystrophin gene cause DMD [Darras et al., 1988], which is characterized by the loss of dystrophin protein and concomitant loss of the entire DAPC. "
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    • "LGMD2C-F Alpha, beta, gamma, delta sarcoglycan Part of dystrophin glycoprotein complex in plasma membrane Delta sarcoglycan: dilated cardiomyopathy [21] [22] LGMD2G Telethonin Sarcomeric localisation [23] LGMD2H TRIM32 Ubiquitin ligase Sarcotubular myopathy, "
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