Phenotypic variability in a Chinese family with rimmed vacuolar distal myopathy

Background: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene mutations have been found in patients with distal myopathy with rimmed vacuoles (DMRV). It is not clear how the same GNE gene mutations can result in different phenotypes in the same family with DMRV. Methods: The clinical, neurophysiological, histopathological, and genetic characteristics of two patients with DMRV from a Chinese family from Taiwan were investigated. Results: Two novel compound heterozygous mutations in different domains of the protein, Ile241Ser in the epimerase and Trp513stop in the kinase domain, were detected in both patients. However, the two patients demonstrated different patterns of disease progression: one had slow disease progression with a typical feature of DMRV (that is, weakness beginning in the distal leg muscles, typically anterior tibialis, with the quadriceps remaining relatively unaffected), and the other had rapid disease progression with an atypical presentation of DMRV. Conclusions: The results of the present study indicate that GNE gene mutations and probably modifier gene(s) or additional factors may result in different phenotypes of DMRV.