Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families

Eur J Neurol. 2018 May;25(5):790-794. doi: 10.1111/ene.13598. Epub 2018 Mar 30.


Background and purpose: The aim was to determine the genetic background of unknown muscular dystrophy in five French families.

Methods: Twelve patients with limb girdle muscular dystrophy or distal myopathy were clinically evaluated. Gene mutations were identified using targeted exon sequencing and mutated DNAJB6 was tested in vitro.

Results: Five patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5 years. Two novel mutations (c.284A>T, p.Asn95Ile, two families; and c.293_295delATG, p.Asp98del, one family) as well as the previously reported c.279C>G (p.Phe93Leu, two families) mutation in DNAJB6 were identified. All showed a reduced capacity to prevent protein aggregation.

Conclusions: The mutational and phenotypical spectrum of DNAJB6-caused muscle disease is larger than previously reported, including also dysphagia. The originally reported c.279C>G (p.Phe93Leu) mutation is now identified in four different populations and appears to be a mutational hotspot. Our report confirms that some DNAJB6 mutations cause distal-onset myopathy and hence DNAJB6 defects should be considered broadly in dominant muscular dystrophy families.

Keywords: genetic and inherited disorders; myopathies; neuromuscular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Distal Myopathies / genetics*
  • Female
  • France
  • HSP40 Heat-Shock Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Chaperones / genetics*
  • Muscle Weakness / genetics
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Phenotype


  • DNAJB6 protein, human
  • HSP40 Heat-Shock Proteins
  • Molecular Chaperones
  • Nerve Tissue Proteins

Supplementary concepts

  • Muscular Dystrophy, Limb-Girdle, Type 1D