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Cardiovasc Res. 2018 Aug 1;114(10):1287-1303. doi: 10.1093/cvr/cvy122.

Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology.

Author information

1
Department of Cardiology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
2
Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo, Pavia, Italy.
3
Department of Translational Medical Sciences, Federico II University, Naples, Italy.
4
Department of Cardiology, Maastricht University Medical Center & CARIM, Maastricht University, Maastricht, The Netherlands.
5
School of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy.
6
School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
7
Department of Systems Physiology, Ruhr University Bochum, Bochum, Germany.
8
Molecular Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
9
Department of Cardiology, Heidelberg University, Heidelberg, Germany.
10
Department of Genetics, Stanford University School of Medicine, Genome Technology Center, Palo Alto, CA, USA.
11
Cardiovascular R&D Unit, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
12
Department of Cardiothoracic Surgery, Hospital of S. João, Porto, Portugal.
13
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
14
Department of Physiology, VU University Medical Centre, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
15
Netherlands Heart Institute, Utrecht, The Netherlands.
16
Cardiovascular Research Center, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK.
17
Department of Cardiovascular Sciences, Leuven University, Leuven, Belgium.

Abstract

Dilated cardiomyopathy (DCM) frequently affects relatively young, economically, and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance-malignancy of the mutated gene-but also on epigenetics, age, toxic factors, pregnancy, and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart.This article is part of the Mini Review Series from the Varenna 2017 meeting of the Working Group of Myocardial Function of the European Society of Cardiology.

PMID:
29800419
PMCID:
PMC6054212
DOI:
10.1093/cvr/cvy122
[Indexed for MEDLINE]
Free PMC Article

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