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Genetics

Broken giant linked to heart failure

Nature volume 483, pages 281–282 (2012)Cite this article

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Genetic mutations can cause a type of heart disease called dilated cardiomyopathy, by predisposing the organ to enlarge and function poorly. It has now been found that 27% of cases are due to mutations that disrupt the muscle protein titin.

Cardiomyopathy — a disorder of heart muscle — is a leading cause of congestive heart failure, in which the organ cannot pump enough blood to meet the body's demands. Mutations account for many cardiomyopathy cases, but most of these gene variants are rare — often described from an individual or a single family1. In particular, mutations associated with a form of the disease known as dilated cardiomyopathy have been identified in about 50 different genes, and the gene most commonly found to be mutated until now (LMNA) explains only 5% of cases. In a landmark study published in the New England Journal of Medicine, Herman et al.2 report that as many as 27% cases, tested using modern sequencing techniques, can be attributed to dominant mutations in the TTN gene, which encodes titin, the largest human protein.

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Figure 1: A molecular ruler.

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Authors and Affiliations

  1. Elizabeth M. McNally is in the Department of Medicine, and in the Department of Human Genetics, Section of Cardiology, University of Chicago, Chicago, Illinois 60637, USA.,

    Elizabeth M. McNally

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  1. Elizabeth M. McNally
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Correspondence to Elizabeth M. McNally.

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The author’s spouse receives patent royalties related to techniques used in massively parallel sequencing.

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McNally, E. Broken giant linked to heart failure. Nature 483, 281–282 (2012). https://doi.org/10.1038/483281a

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