Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation

Eur J Hum Genet. 2012 Sep;20(9):984-5. doi: 10.1038/ejhg.2012.39. Epub 2012 Mar 7.


Using exome sequencing we searched for the genetic cause of autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy (ARVC) in a Swedish family. A heterozygous C-to-T transition, c.1255C>T, p.Pro419Ser in the desmin gene on chromosome 2q35, was identified. Previous studies had demonstrated linkage to chromosome 10q22.3, but no causative mutation had been found in that region. Sanger sequencing of DNA from 17 family members confirmed the heterozygous c.1255C>T desmin mutation in seven out of ten family members that had been classified as affected in the previous study. Our new results demonstrate the usefulness of next-generation sequencing, and the diagnostic difficulties with some forms of dominantly inherited muscle diseases as they can display a wide clinical and morphological variability even within a given family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arrhythmogenic Right Ventricular Dysplasia / complications
  • Arrhythmogenic Right Ventricular Dysplasia / diagnosis
  • Arrhythmogenic Right Ventricular Dysplasia / genetics*
  • Chromosomes, Human, Pair 2
  • Desmin / genetics*
  • European Continental Ancestry Group / genetics*
  • Exome
  • Female
  • Heterozygote
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intermediate Filaments / genetics*
  • Male
  • Middle Aged
  • Muscular Dystrophies / complications
  • Muscular Dystrophies / diagnosis
  • Muscular Dystrophies / genetics*
  • Pedigree
  • Point Mutation*
  • Sweden


  • Desmin

Supplementary concepts

  • Filaminopathy, autosomal dominant