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Genetics of Dilated Cardiomyopathy: Clinical Implications

  • Myocardial Disease (A Abbate, Section Editor)
  • Published:
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Abstract

Purpose of Review

This review aims to summarize the current knowledge on the genetic background of dilated cardiomyopathy (DCM), with particular attention to the genotype-phenotype correlations and the possible implications for clinical management.

Recent Findings

Next generation sequencing (NGS) has led to the identification of an increasing number of genes and mutations responsible for DCM. This genetic variability is probably related to the extreme heterogeneity of disease manifestation. Important findings have associated mutations of Lamin A/C (LMNA) and Filamin C (FLNC) to poor prognosis and the propensity to cause an arrhythmic phenotype, respectively. However, a deeper understanding of the genotype-phenotype correlation is necessary, because it could have several implications for the clinical management of the patients. Furthermore, the correct interpretation of pathogenicity of mutations and the clinical impact of genetic testing in DCM patients still represent important fields to be implemented.

Summary

A pathogenic gene mutation can be identified in almost 40% of DCM patients. The recent discoveries and future research in the field of genotype-phenotype correlation may lead to a more personalized management of the mutation carriers towards the application of precision medicine in DCM.

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Abbreviations

ARVC:

Right ventricular arrhythmogenic cardiomyopathy

DCM:

Dilated cardiomyopathy

DES:

Desmin

DMD:

Dystrophin

DSP:

Desmoplakin

FLNC :

Filamin C

HCM:

Hypertrophic cardiomyopathy

ICD:

Implantable cardioverter defibrillator

LDB3:

LIM domain binding 3

LMNA:

Lamin A/C

LVEF:

Left ventricular ejection fraction

LVRR:

Left ventricular reverse remodeling

MYH7:

Beta myosin heavy chain

MYBPC3:

Myosin binding protein C3

MYPN:

Myopalladin

NEBL:

Nebulette

NEXN:

Nexilin F-actin binding protein

NGS:

Next generation sequencing

OBSL1:

Obscurin like 1

RBM20:

RNA-binding motif protein-20

RCM:

Restrictive cardiomyopathy

SCD:

Sudden cardiac death

SCN5A:

Sodium channel protein type 5 subunit alpha

TNNT2:

Cardiac troponin T2

TPM1:

Tropomyosin

TTN:

Titin

VUS:

Variant of uncertain significance

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Author notes

  1. A. Paldino and G. De Angelis equally contributed as first author.

Authors and Affiliations

  1. Cardiovascular Department, Azienda Sanitaria Universitaria Integrata and University of Trieste (ASUITs), Via P. Valdoni, 7, 34100, Trieste, Italy

    A. Paldino, G. De Angelis, M. Merlo, M. Gigli, M. Dal Ferro & G. Sinagra

  2. Medical Genetics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy

    G. M. Severini

  3. Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    L. Mestroni

Authors
  1. A. Paldino
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  2. G. De Angelis
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  3. M. Merlo
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  4. M. Gigli
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  5. M. Dal Ferro
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  6. G. M. Severini
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  7. L. Mestroni
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  8. G. Sinagra
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Corresponding author

Correspondence to M. Merlo.

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Conflict of Interest

Alessia Paldino, Giulia De Angelis, Marco Merlo, Marta Gigli, Matteo Dal Ferro, Giovanni Maria Severini, Luisa Mestroni and Gianfranco Sinagra declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Myocardial Disease

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Paldino, A., De Angelis, G., Merlo, M. et al. Genetics of Dilated Cardiomyopathy: Clinical Implications. Curr Cardiol Rep 20, 83 (2018). https://doi.org/10.1007/s11886-018-1030-7

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  • DOI: https://doi.org/10.1007/s11886-018-1030-7

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