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Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations
Jens Mogensen, … , Perry Elliott, William J. McKenna
Jens Mogensen, … , Perry Elliott, William J. McKenna
Published January 15, 2003
Citation Information: J Clin Invest. 2003;111(2):209-216. https://doi.org/10.1172/JCI16336.
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Article Cardiology

Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations

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Abstract

Restrictive cardiomyopathy (RCM) is an uncommon heart muscle disorder characterized by impaired filling of the ventricles with reduced volume in the presence of normal or near normal wall thickness and systolic function. The disease may be associated with systemic disease but is most often idiopathic. We recognized a large family in which individuals were affected by either idiopathic RCM or hypertrophic cardiomyopathy (HCM). Linkage analysis to selected sarcomeric contractile protein genes identified cardiac troponin I (TNNI3) as the likely disease gene. Subsequent mutation analysis revealed a novel missense mutation, which cosegregated with the disease in the family (lod score: 4.8). To determine if idiopathic RCM is part of the clinical expression of TNNI3 mutations, genetic investigations of the gene were performed in an additional nine unrelated RCM patients with restrictive filling patterns, bi-atrial dilatation, normal systolic function, and normal wall thickness. TNNI3 mutations were identified in six of these nine RCM patients. Two of the mutations identified in young individuals were de novo mutations. All mutations appeared in conserved and functionally important domains of the gene.

Authors

Jens Mogensen, Toru Kubo, Mauricio Duque, William Uribe, Anthony Shaw, Ross Murphy, Juan R. Gimeno, Perry Elliott, William J. McKenna

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Figure 3

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Schematic representation of the human cardiac troponin I gene with the n...
Schematic representation of the human cardiac troponin I gene with the number of corresponding amino acids encoded by the gene and interaction sites with other sarcomeric contractile proteins (13, 28). The stars indicate mutations identified in patients with restrictive cardiomyopathy in numerical order: Leu144Gln identified in H38, Arg145Trp identified in H816 and H805, Ala171Thr identified in H974, Lys178Glu identified in H906, Asp190His identified in H640, and Arg192His identified in H417.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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