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Role of titin in cardiomyopathy: from DNA variants to patient stratification

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Title: Role of titin in cardiomyopathy: from DNA variants to patient stratification
Authors: Ware, JS
Cook, SA
Item Type: Journal Article
Abstract: Dilated cardiomyopathy (DCM) affects approximately 1 in 250 individuals and is the leading indication for heart transplantation. DCM is often familial, and the most common genetic predisposition is a truncating variation in the giant sarcomeric protein, titin, which occurs in up to 15% of ambulant patients with DCM and 25% of end-stage or familial cases. In this article, we review the evidence for the role of titin truncation in the pathogenesis of DCM and our understanding of the molecular mechanisms and pathophysiological consequences of variation in the gene encoding titin (TTN). Such variation is common in the general population (up to 1% of individuals), and we consider key features that discriminate variants with disease-causing potential from those that are benign. We summarize strategies for clinical interpretation of genetic variants for use in the diagnosis of patients and the evaluation of their relatives. Finally, we consider the contemporary and potential future role for genetic stratification in cardiomyopathy and in the general population, evaluating titin variation as a predictor of outcome and treatment response for precision medicine.
Issue Date: 14-Dec-2017
Date of Acceptance: 14-Dec-2017
URI: http://hdl.handle.net/10044/1/55445
DOI: https://dx.doi.org/10.1038/nrcardio.2017.190
ISSN: 1759-5002
Publisher: Nature Publishing Group
Start Page: 241
End Page: 252
Journal / Book Title: Nature Reviews Cardiology
Volume: 15
Copyright Statement: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Sponsor/Funder: British Heart Foundation
Wellcome Trust
Funder's Grant Number: SP/10/10/28431
107469/Z/15/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
FAMILIAL DILATED CARDIOMYOPATHY
CAUSE HYPERTROPHIC CARDIOMYOPATHY
EARLY RESPIRATORY-FAILURE
CARDIOLOGY WORKING GROUP
NONSENSE-MEDIATED DECAY
MUSCLE FILAMENT TITIN
PROTEIN-C GENE
EUROPEAN-SOCIETY
HEART-FAILURE
FAILING HEART
Cardiovascular System & Hematology
Publication Status: Published
Open Access location: http://rdcu.be/Boxd
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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