Desmin mutations as a cause of right ventricular heart failure affect the intercalated disks

Ellen Otten, Angeliki Asimaki, Alexander Maass, Irene M. van Langen, Allard van der Wal, Nicolaas de Jonge, Maarten P. van den Berg, Jeffrey E. Saffitz, Arthur A. M. Wilde, Jan D. H. Jongbloed, J. Peter van Tintelen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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BACKGROUND Mutations in the gene encoding desmin (DES), an intermediate filament protein, underlie a heterogeneous phenotype, which is referred to as desmin-related myopathy (DRM). Right ventricular involvement including an arrhythmogenic right ventricular cardiomyopathy (ARVC)(-like) phenotype has occasionally been described in DES mutation-carrying patients.

OBJECTIVE To determine the effects of a DES missense mutation on the structure of different intercalated disk proteins, to evaluate right ventricular involvement in DES mutation carriers, and to establish the role of DES mutations in ARVC(-like) phenotypes.

METHODS We evaluated the clinical phenotype in two families carrying two different DES mutations. One family was diagnosed with DRM, with an ARVC(-like) phenotype in one patient, while the other family presented with a severe biventricular cardiomyopathy. Additional immunohistochemistry of desmosomal proteins was performed in myocardial tissue from two patients of the last family. The DES gene was screened for mutations in 50 ARVC(-like) patients.

RESULTS Except for two different DES mutations (p.N342D and p.R454W) in two families with DRM and severe biventricular cardiomyopathy, respectively, we did not find additional DES mutations in ARVC(-like) patients. In addition to desmin aggregates, immunohistochemistry demonstrated a decreased amount of desmoplakin and plakophilin-2 at the intercalated disk in p.R454W mutation carriers.

CONCLUSIONS We confirmed that either an ARVC-like phenotype or a severe cardiomyopathy with right ventricular involvement are possible, yet infrequent, cardiac phenotypes in DRM. Moreover, we demonstrated that the DES mutation p. R454W affects the localization of desmoplakin and plakophilin-2 at the intercalated disk, suggesting a link between desmosomal cardiomyopathies (mainly affecting the right ventricle) and cardiomyopathies caused by DES mutations.

Original languageEnglish
Pages (from-to)1058-1064
Number of pages7
JournalHeart Rhythm
Issue number8
Publication statusPublished - Aug-2010


  • Cardiomyopathy
  • Intercalated disk
  • Genes
  • Genetics
  • Immunohistochemistry
  • Right ventricle
  • Desmin
  • GENE

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