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Biophysical Reviews

, Volume 10, Issue 4, pp 983–1006 | Cite as

Molecular insights into cardiomyopathies associated with desmin (DES) mutations

  • Andreas Brodehl
  • Anna Gaertner-Rommel
  • Hendrik Milting
Review

Abstract

Increasing usage of next-generation sequencing techniques pushed during the last decade cardiogenetic diagnostics leading to the identification of a huge number of genetic variants in about 170 genes associated with cardiomyopathies, channelopathies, or syndromes with cardiac involvement. Because of the biochemical and cellular complexity, it is challenging to understand the clinical meaning or even the relevant pathomechanisms of the majority of genetic sequence variants. However, detailed knowledge about the associated molecular pathomechanism is essential for the development of efficient therapeutic strategies in future and genetic counseling. Mutations in DES, encoding the muscle-specific intermediate filament protein desmin, have been identified in different kinds of cardiac and skeletal myopathies. Here, we review the functions of desmin in health and disease with a focus on cardiomyopathies. In addition, we will summarize the genetic and clinical literature about DES mutations and will explain relevant cell and animal models. Moreover, we discuss upcoming perspectives and consequences of novel experimental approaches like genome editing technology, which might open a novel research field contributing to the development of efficient and mutation-specific treatment options.

Keywords

Desmin Cardiomyopathy Desminopathy Cardiovascular genetics Intermediate filaments 

Abbreviations

ACM

Arrhythmogenic cardiomyopathy

ACMG

American College of Medical Genetics and Genomics

AF

Atrial fibrillation

AFM

Atomic force microscopy

ALVC

Arrhythmogenic left ventricular cardiomyopathy

ARVC

Arrhythmogenic right ventricular cardiomyopathy

aSNOM

Apertureless scanning near-field microscopy

ATP

Adenosine triphosphate

AVB

Atrioventricular block

CM

Cardiomyopathy

DCM

Dilated cardiomyopathy

DRM

Desmin-related myopathy

DSC2

Desmocollin-2

DSG2

Desmoglein-2

DSP

Desmoplakin

EPR

Electron paramagnetic resonance

GFAP

Glial fibrillary acidic protein

GGA

Geranylgeranylacetone

HCM

Hypertrophic cardiomyopathy

HOCM

Hypertrophic obstructive cardiomyopathy

HTx

Heart transplantation

IF

Intermediate filament

LAFB

Left anterior fascicular block

LBBB

Left bundle-branched block

LGMD

Limb-girdle muscular dystrophy

LVNC

Left ventricular noncompaction cardiomyopathy

LW

Limp weakness

MAF

Minor allele frequency

MFM

Myofibrillar myopathy

MRI

Magnetic resonance imaging

NCM

Noncompaction cardiomyopathy

NMD

Nonsense-mediated RNA decay

PG

Plakoglobin

PKP2

Plakophilin-2

PTC

Premature termination codon

PTM

Posttranslational modification

RBBB

Right bundle-branched block

RCM

Restrictive cardiomyopathy

SCD

Sudden cardiac death

SM

Skeletal myopathy

SMD

Smooth muscle defect

SNP

Single nucleotide polymorphism

SQTS

Short QT syndrome

TAC

Transverse aortic constriction

TEM

Transmission electron microscopy

ULF

Unit length filament

VUS

Variant of unknown significance

Notes

Acknowledgements

The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. We thank Dr. Volker Walhorn (Experimental Biophysics and Applied Nanoscience, Faculty of Physics and Bielefeld Institute for Biophysics and Nanoscience (BINAS), Bielefeld University, Germany) for providing Fig. 5e.

Compliance with ethical standards

Funding

AB received a grant of the German Society of Heart Research (DSHF, F/07/17) and a grant of the University Bielefeld (Reseach fond OWL). AGR is supported by the Medical Faculty of the Ruhr-University Bochum (FoRUM). HM is thankful for funding of the German Research Foundation (DFG, MI 1146/2-1) and the Erich and Hanna Klessmann Foundation (Gütersloh, Germany).

Conflicts of interest

Andreas Brodehl declares that he has no conflicts of interest. Anna Gaertner-Rommel declares that she has no conflicts of interest. Hendrik Milting declares that he has no conflicts of interest.

Ethical approval

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

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© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Erich and Hanna Klessmann Institute for Cardiovascular Research & Development, Heart and Diabetes Centre NRWRuhr-University BochumBad OeynhausenGermany

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