Limb-girdle phenotype is frequent in patients with myopathy associated with GNE mutations

Abstract The gene GNE encodes a bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Its mutations are found in distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM). Those disorders are characterized clinically by predominant anterior tibial muscle weakness and atrophy, and pathologically by rimmed vacuoles on muscle biopsy. We analyzed 11 Korean patients with GNE mutations. The mutations showed ethnic similarity to those of Japanese patients, showing the highest frequency with V572L. Another mutation of C13S was also found recurring in our patient group. Interestingly, about half of the patients showed limb-girdle myopathy rather than distal myopathy. This was further represented by limb muscle CT scans revealing atrophic hamstring and relatively spared anterior tibial muscle. However, quadriceps muscles were consistently spared both in distal and limb-girdle phenotypes. In conclusion, this study demonstrates a phenotypic diversity associated with GNE mutations. Recognizing a wider clinical spectrum of GNE mutations will help benefit more patients with imminent new therapy.