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Unraveling obscurins in heart disease

  • Alyssa Grogan
  • Aikaterini Kontrogianni-Konstantopoulos
Invited Review
  • 136 Downloads

Abstract

Obscurins, expressed from the single OBSCN gene, are a family of giant, modular, cytoskeletal proteins that play key structural and regulatory roles in striated muscles. They were first implicated in the development of heart disease in 2007 when two missense mutations were found in a patient diagnosed with hypertrophic cardiomyopathy (HCM). Since then, the discovery of over a dozen missense, frameshift, and splicing mutations that are linked to various forms of cardiomyopathy, including HCM, dilated cardiomyopathy (DCM), and left ventricular non-compaction (LVNC), has highlighted OBSCN as a potential disease-causing gene. At this time, the functional consequences of the identified mutations remain largely elusive, and much work has yet to be done to characterize the disease mechanisms of pathological OBSCN variants. Herein, we describe the OBSCN mutations known to date, discuss their potential impact on disease development, and provide future directions in order to better understand the involvement of obscurins in heart disease.

Keywords

Obscurin Sarcomeric mutations Cardiomyopathy Heart failure 

Notes

Funding information

This work was supported by grants from the American Heart Association (16GRNT31290010 to AKK), Muscular Dystrophy Association (313579 to AKK), and NIH/MIAMS (T32AR7592 to AG).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Maryland School of MedicineBaltimoreUSA

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