Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from theworking group of myocardial function of the European Society of Cardiology

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

Research output: Contribution to journalReview articleAcademicpeer-review

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
JournalCardiovascular Research
Volume114
Issue number10
DOIs
Publication statusPublished - 2018

Cite this

Bondue, Antoine ; Arbustini, Eloisa ; Bianco, Anna ; Ciccarelli, Michele ; Dawson, Dana ; de Rosa, Matteo ; Hamdani, Nazha ; Hilfiker-Kleiner, Denise ; Meder, Benjamin ; Leite-Moreira, Adelino F. ; Thum, Thomas ; Tocchetti, Carlo G. ; Varricchi, Gilda ; van der Velden, Jolanda ; Walsh, Roddy ; Heymans, Stephane. / Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from theworking 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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title = "Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from theworking group of myocardial function of the European Society of Cardiology",
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.",
keywords = "Dilated Cardiomyopathy, Genetics, Genome-environment interaction",
author = "Antoine Bondue and Eloisa Arbustini and Anna Bianco and Michele Ciccarelli and Dana Dawson and {de Rosa}, Matteo and Nazha Hamdani and Denise Hilfiker-Kleiner and Benjamin Meder and Leite-Moreira, {Adelino F.} and Thomas Thum and Tocchetti, {Carlo G.} and Gilda Varricchi and {van der Velden}, Jolanda and Roddy Walsh and Stephane Heymans",
year = "2018",
doi = "10.1093/cvr/cvy122",
language = "English",
volume = "114",
pages = "1287--1303",
journal = "Cardiovascular Research",
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Bondue, A, Arbustini, E, Bianco, A, Ciccarelli, M, Dawson, D, de Rosa, M, Hamdani, N, Hilfiker-Kleiner, D, Meder, B, Leite-Moreira, AF, Thum, T, Tocchetti, CG, Varricchi, G, van der Velden, J, Walsh, R & Heymans, S 2018, 'Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from theworking 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, https://doi.org/10.1093/cvr/cvy122

Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from theworking group of myocardial function of the European Society of Cardiology. / Bondue, Antoine; Arbustini, Eloisa; Bianco, Anna; Ciccarelli, Michele; Dawson, Dana; de Rosa, Matteo; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Meder, Benjamin; Leite-Moreira, Adelino F.; Thum, Thomas; Tocchetti, Carlo G.; Varricchi, Gilda; van der Velden, Jolanda; Walsh, Roddy; Heymans, Stephane.

In: Cardiovascular Research, Vol. 114, No. 10, 2018, p. 1287-1303.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from theworking group of myocardial function of the European Society of Cardiology

AU - Bondue, Antoine

AU - Arbustini, Eloisa

AU - Bianco, Anna

AU - Ciccarelli, Michele

AU - Dawson, Dana

AU - de Rosa, Matteo

AU - Hamdani, Nazha

AU - Hilfiker-Kleiner, Denise

AU - Meder, Benjamin

AU - Leite-Moreira, Adelino F.

AU - Thum, Thomas

AU - Tocchetti, Carlo G.

AU - Varricchi, Gilda

AU - van der Velden, Jolanda

AU - Walsh, Roddy

AU - Heymans, Stephane

PY - 2018

Y1 - 2018

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.

AB - 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.

KW - Dilated Cardiomyopathy

KW - Genetics

KW - Genome-environment interaction

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UR - https://www.ncbi.nlm.nih.gov/pubmed/29800419

U2 - 10.1093/cvr/cvy122

DO - 10.1093/cvr/cvy122

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EP - 1303

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

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