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.

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; Ciccarelli, Michele; Dawson, Dana; De Rosa, Matteo; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Meder, Benjamin; Leite Moreira, Adelino; Thum, Thomas; Tocchetti, Carlo G; Varricchi, Gilda; Van der Velden, Jolanda; Walsh, Roddy; Heymans, Stephane. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - (2018). [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

Bianco, Anna;Ciccarelli, Michele;Tocchetti, Carlo G;Varricchi, Gilda;Heymans, Stephane
2018

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.
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 / Bondue, Antoine; Arbustini, Eloisa; Bianco, Anna; Ciccarelli, Michele; Dawson, Dana; De Rosa, Matteo; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Meder, Benjamin; Leite Moreira, Adelino; Thum, Thomas; Tocchetti, Carlo G; Varricchi, Gilda; Van der Velden, Jolanda; Walsh, Roddy; Heymans, Stephane. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - (2018). [10.1093/cvr/cvy122]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/718957
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