Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy

Neurology. 2002 Dec 10;59(11):1689-93. doi: 10.1212/01.wnl.0000041631.28557.c6.


Background: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE).

Objective: To determine whether DMRV and HIBM are allelic.

Methods: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured.

Results: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity.

Conclusions: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.

MeSH terms

  • Alleles
  • Carbohydrate Epimerases / genetics*
  • DNA / genetics
  • DNA / isolation & purification
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli Proteins*
  • Genetic Linkage / genetics
  • Genetic Testing
  • Humans
  • Leukocytes / enzymology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / ultrastructure
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology*
  • Mutation / genetics
  • Myositis, Inclusion Body / enzymology
  • Myositis, Inclusion Body / genetics*
  • Myositis, Inclusion Body / pathology*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Vacuoles / ultrastructure


  • Escherichia coli Proteins
  • DNA
  • Phosphotransferases (Alcohol Group Acceptor)
  • N-acylmannosamine kinase
  • Carbohydrate Epimerases
  • UDP acetylglucosamine-2-epimerase
  • wecB protein, E coli