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

Antoine Bondue, Eloisa Arbustini, Anna M Bianco, Michele Ciccarelli, Dana Dawson, Matteo De Rosa, Nazha Hamdani, Denise Hilfiker-Kleiner, Benjamin Meder, Adelino Leite Moreira, Thomas Thum, Carlo Gabriele Tocchetti, Gilda Varricchi, Jolanda Van der Velden, Roddy Walsh, Stephane Heymans

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1287-1303
Number of pages18
JournalCardiovascular Research
Volume114
Issue number10
Early online date23 May 2018
DOIs
Publication statusPublished - 1 Aug 2018

Fingerprint

Dilated Cardiomyopathy
Genotype
Phenotype
Genes
Mutation
Heart Failure
Penetrance
Poisons
Age Factors
Anti-Arrhythmia Agents
Gene Silencing
Heart Transplantation
Epigenomics
Small Interfering RNA
Heart Diseases
Fibrosis
Observation
Inflammation
Calcium
Morbidity

Keywords

  • Journal Article
  • dilated cardiomyopathy
  • genetics
  • genome-environment interaction

Cite this

Complex roads from genotype to phenotype in dilated cardiomyopathy : scientific update from the Working Group of Myocardial Function of the European Society of Cardiology. / Bondue, Antoine; Arbustini, Eloisa; Bianco, Anna M; Ciccarelli, Michele; Dawson, Dana; De Rosa, Matteo; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Meder, Benjamin; Leite Moreira, Adelino; Thum, Thomas; Gabriele Tocchetti, Carlo; Varricchi, Gilda; Van der Velden, Jolanda; Walsh, Roddy; Heymans, Stephane.

In: Cardiovascular Research, Vol. 114, No. 10, 01.08.2018, p. 1287-1303.

Research output: Contribution to journalArticle

Bondue, A, Arbustini, E, Bianco, AM, Ciccarelli, M, Dawson, D, De Rosa, M, Hamdani, N, Hilfiker-Kleiner, D, Meder, B, Leite Moreira, A, Thum, T, Gabriele Tocchetti, C, Varricchi, G, Van der Velden, J, Walsh, R & Heymans, S 2018, 'Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology' Cardiovascular Research, vol. 114, no. 10, pp. 1287-1303. https://doi.org/10.1093/cvr/cvy122
Bondue, Antoine ; Arbustini, Eloisa ; Bianco, Anna M ; Ciccarelli, Michele ; Dawson, Dana ; De Rosa, Matteo ; Hamdani, Nazha ; Hilfiker-Kleiner, Denise ; Meder, Benjamin ; Leite Moreira, Adelino ; Thum, Thomas ; Gabriele Tocchetti, Carlo ; Varricchi, Gilda ; Van der Velden, Jolanda ; Walsh, Roddy ; Heymans, Stephane. / Complex roads from genotype to phenotype in dilated cardiomyopathy : scientific update from the Working Group of Myocardial Function of the European Society of Cardiology. In: Cardiovascular Research. 2018 ; Vol. 114, No. 10. pp. 1287-1303.
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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.",
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AU - De Rosa, Matteo

AU - Hamdani, Nazha

AU - Hilfiker-Kleiner, Denise

AU - Meder, Benjamin

AU - Leite Moreira, Adelino

AU - Thum, Thomas

AU - Gabriele Tocchetti, Carlo

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AU - Van der Velden, Jolanda

AU - Walsh, Roddy

AU - Heymans, Stephane

N1 - The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, with support of the Dutch Heart Foundation, CVON2011-ARENA, CVON2018-ARENA PRIME, CVON2016-Early HFPEF, and CVON 2017-ShePREDICTS to S.H.

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N2 - 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.

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