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.
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 DMRVpatients was also measured. RESULTS: The authors identified 27 unrelated DMRVpatients with homozygous or compound-heterozygous mutations in the GNE gene. DMRVpatients 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.
Authors: N C Voermans; M Guillard; R Doedée; M Lammens; M Huizing; G W Padberg; R A Wevers; B G van Engelen; D J Lefeber Journal: Clin Neuropathol Date: 2010 Mar-Apr Impact factor: 1.368
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