Patient-specific induced-pluripotent stem cells-derived cardiomyocytes recapitulate the pathogenic phenotypes of dilated cardiomyopathy due to a novel DES mutation identified by whole exome sequencing

Hum Mol Genet. 2013 Apr 1;22(7):1395-403. doi: 10.1093/hmg/dds556. Epub 2013 Jan 8.


In this paper, we report a novel heterozygous mutation of A285V codon conversion on exon 4 of the desmin (DES), using whole exome sequencing (WES) in an isolated proband with documented dilated cardiomyopathy (DCM). This mutation is predicted to cause three-dimensional structure changes of DES. Immunohistological and electron microscopy studies demonstrated diffuse abnormal DES aggregations in DCM-induced-pluripotent stem cell (iPSC)-derived cardiomyocytes, and control-iPSC-derived cardiomyocytes transduced with A285V-DES. DCM-iPSC-derived cardiomyocytes also exhibited functional abnormalities in vitro. This is the first demonstration that patient-specific iPSC-derived cardiomyocytes can be used to provide histological and functional confirmation of a suspected genetic basis for DCM identified by WES.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Cardiomyopathy, Dilated / diagnostic imaging
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / physiopathology
  • Cell Differentiation
  • Desmin / chemistry
  • Desmin / genetics*
  • Desmin / metabolism
  • Exome
  • Exons
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Male
  • Molecular Sequence Data
  • Mutation, Missense
  • Myocytes, Cardiac / metabolism*
  • Pedigree
  • Phenotype
  • Sequence Analysis, DNA
  • Stroke Volume / genetics
  • Ultrasonography
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / physiopathology


  • Desmin