Genetic Characterization of a French Cohort of GNE-mutation negative inclusion body myopathy patients with exome sequencing

Muscle Nerve. 2017 Nov;56(5):993-997. doi: 10.1002/mus.25638. Epub 2017 Apr 7.


Introduction: Hereditary inclusion body myopathy (hIBM) refers to a group of clinically and genetically heterogeneous diseases. The overlapping histochemical features of hIBM with other genetic disorders lead to low diagnostic rates with targeted single-gene sequencing. This is true for the most prevalent form of hIBM, GNEpathy. Therefore, we used whole-exome sequencing (WES) to determine whether a cohort of clinically suspected GNEpathy patients undiagnosed by targeted GNE analysis could be genetically characterized.

Methods: Twenty patients with hIBM but undiagnosed by targeted GNE sequencing were analyzed by WES before data filtering on 306 genes associated with neuromuscular disorders.

Results: Seven patients out of 20 were found to have disease-causing mutations in genes associated with hIBM or genes allowing for hIBM in the differential diagnosis or associated with unexpected diagnosis.

Discussion: Next-generation sequencing is an efficient strategy in the context of hIBM, resulting in a molecular diagnosis for 35% of the patients initially undiagnosed by targeted GNE analysis. Muscle Nerve 56: 993-997, 2017.

Keywords: GNE; NGS; diagnosis; exome; hIBM; myopathy.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • DNA Mutational Analysis
  • Exome
  • Female
  • France
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Mutation / genetics*
  • Myositis, Inclusion Body / genetics*
  • Phenotype


  • Multienzyme Complexes
  • UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase