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Cardiac and skeletal actin gene mutations are not a common cause of dilated cardiomyopathy
  1. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK

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Editor—Idiopathic dilated cardiomyopathy (DCM) is a primary disorder of heart muscle that is characterised by dilatation and impaired contraction of the chambers of the heart. Presentation is usually with heart failure, which is progressive, with a five year mortality of 50% after the onset of symptoms. Since the cause of this condition is unknown, specific therapy is not possible, and heart transplantation is the only definitive treatment for end stage disease.

A major advance in the study of the pathogenesis of DCM has been the demonstration that 20-30% of cases are familial, suggesting that genetic factors may be involved in the aetiology of the condition.1 Reported families most commonly are compatible with autosomal dominant inheritance, but some with X linked and autosomal recessive inheritance have been documented. Genetic linkage studies in single large dominant pedigrees have implicated seven different chromosomal loci, underlining the genetic heterogeneity of the condition.2-4

Recently, missense mutations in the cardiac alpha actin gene that appeared to cosegregate with DCM were identified in two unrelated small families, raising the possibility that proteins involved in the generation or transmission of force in cardiac myocytes may be involved in the pathogenesis of DCM.5 The evidence in favour of a pathological role was confined to the conservation of the affected residues and the absence of the mutations from a large series of controls (870 chromosomes) (without unequivocal evidence of linkage or a functional deficit induced by the mutations). In addition, the prevalence of cardiac actin mutations in DCM is unknown. Furthermore, cardiac and skeletal actin genes are coexpressed in the heart, and the skeletal isoform, …

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