GroganPflugersArchiv'18.pdf

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