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Heart failure mutation
Genome Biology volume 4, Article number: spotlight-20030305-01 (2003)
Heart failure is a major cause of death in the developed world and a growing health-care concern. In the February 28 Science Schmitt et al. report the discovery of a mutation in patients suffering from inherited dilated cardiomyopathy with refractory congestive heart disease (Science 2003, 299:1410-1413). A dominant missense mutation (Arg→Cys) was found at residue 9 in phospholamban (PLN). Phospholamban is a 52 amino-acid transmembrane phosphoprotein that regulates the Ca2+ ATPase pump (SERCA2a). Schmitt et al. generated transgenic mice expressing the mutant PLNR9C in the heart and observed biventral cardiac dilation and progressive cardiomyopathy resembling the human symptoms. Tissue culture experiments demonstrated that the PLNR9C mutant form trapped protein kinase A (PKA), which led to inhibition of the phosphorylation of wild-type PLNWT protein and delayed decay of Ca2+ transients. Manipulating Ca2+ handling and/or PLN activity may provide a therapeutic opportunity for treating human heart disease.
Recent advances in understanding the genetic etiology of congenital heart disease.
Phospholamban and cardiac contractility.
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Weitzman, J.B. Heart failure mutation. Genome Biol 4, spotlight-20030305-01 (2003). https://doi.org/10.1186/gb-spotlight-20030305-01
- Heart Failure
- Missense Mutation
- Dilate Cardiomyopathy
- Human Heart