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

Shinichi Tsubata, Karla R. Bowles, Matteo Vatta, Carmelann Zintz, Jack Titus, Linda Muhonen, Neil E. Bowles, Jeffrey Towbin

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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 δ-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 δ-sarcoglycan staining. No skeletal muscle disease occurred in any of these patients. These data suggest that δ-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.

Original languageEnglish (US)
Pages (from-to)655-662
Number of pages8
JournalJournal of Clinical Investigation
Volume106
Issue number5
DOIs
StatePublished - Jan 1 2000

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Sarcoglycans
Dilated Cardiomyopathy
Mutation
Genes
Dystrophin-Associated Protein Complex
Lamin Type A
Nucleic Acid Conformation
Sarcolemma
Dystrophin
Desmin
Familial dilated cardiomyopathy
Single-Stranded DNA
Cytoskeleton
DNA Sequence Analysis
Fluorescent Antibody Technique
Actins
Myocardium
Skeletal Muscle
Staining and Labeling
Morbidity

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Mutations in the human δ-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. / Tsubata, Shinichi; Bowles, Karla R.; Vatta, Matteo; Zintz, Carmelann; Titus, Jack; Muhonen, Linda; Bowles, Neil E.; Towbin, Jeffrey.

In: Journal of Clinical Investigation, Vol. 106, No. 5, 01.01.2000, p. 655-662.

Research output: Contribution to journalArticle

Tsubata, S, Bowles, KR, Vatta, M, Zintz, C, Titus, J, Muhonen, L, Bowles, NE & Towbin, J 2000, 'Mutations in the human δ-sarcoglycan gene in familial and sporadic dilated cardiomyopathy', Journal of Clinical Investigation, vol. 106, no. 5, pp. 655-662. https://doi.org/10.1172/JCI9224
Tsubata, Shinichi ; Bowles, Karla R. ; Vatta, Matteo ; Zintz, Carmelann ; Titus, Jack ; Muhonen, Linda ; Bowles, Neil E. ; Towbin, Jeffrey. / Mutations in the human δ-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. In: Journal of Clinical Investigation. 2000 ; Vol. 106, No. 5. pp. 655-662.
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