Beyond the Cardiac Myofilament: Hypertrophic Cardiomyopathy- Associated Mutations in Genes that Encode Calcium-Handling Proteins

Author(s): A. P. Landstrom, M. J. Ackerman.

Journal Name: Current Molecular Medicine

Volume 12 , Issue 5 , 2012

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Abstract:

Traditionally regarded as a genetic disease of the cardiac sarcomere, hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and a significant cause of sudden cardiac death. While the most common etiologies of this phenotypically diverse disease lie in a handful of genes encoding critical contractile myofilament proteins, approximately 50% of patients diagnosed with HCM worldwide do not host sarcomeric gene mutations. Recently, mutations in genes encoding calcium-sensitive and calciumhandling proteins have been implicated in the pathogenesis of HCM. Among these are mutations in TNNC1- encoded cardiac troponin C, PLN-encoded phospholamban, and JPH2-encoded junctophilin 2 which have each been associated with HCM in multiple studies. In addition, mutations in RYR2-encoded ryanodine receptor 2, CASQ2-encoded calsequestrin 2, CALR3-encoded calreticulin 3, and SRI-encoded sorcin have been associated with HCM, although more studies are required to validate initial findings. While a relatively uncommon cause of HCM, mutations in genes that encode calcium-handling proteins represent an emerging genetic subset of HCM. Furthermore, these naturally occurring disease-associated mutations have provided useful molecular tools for uncovering novel mechanisms of disease pathogenesis, increasing our understanding of basic cardiac physiology, and dissecting important structure-function relationships within these proteins.

Keywords: Calcium, genetics, hypertrophic cardiomyopathy, junctophilin, mutation, phospholamban, troponin.

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Article Details

VOLUME: 12
ISSUE: 5
Year: 2012
Page: [507 - 518]
Pages: 12
DOI: 10.2174/156652412800620020
Price: $58

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