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Pediatric and adult-onset HCM mutations in the myosin motor domain have similar properties

Pre-print. 2019; 
Carlos D Vera,#, Chloe A Johnson,#, Jonathan Walklate , Arjun Adhikari , Zoltan Ujfalusi , Marina Svicevic , Srba M Mijailovich , Ariana Combs , Stephen J. Langer , Kathleen M. Ruppel , James A. Spudich , Leslie A. Leinwand,*, and Michael A. Geeves
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摘要

Hypertrophic Cardiomyopathy (HCM) is a common genetic disorder that typically involves left ventricular hypertrophy and abnormal cardiac contractility. Mutations in β- MyHC are a major cause of HCM and are typically characterized with cardiac hypercontractility, but the specific mechanistic changes to myosin function that lead to the disease remain incompletely understood. Predicting the severity of any single β-MyHC mutation is hindered by a lack of detailed evaluation at the molecular level. In addition, since the cardiomyopathy can take 20 - 40 years to develop, the severity of the mutations must be somewhat subtle. We hypothesized that mutations which result in childhood cardiomyopathies may show a more s... More

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