Novel Mutations of theGNEGene in Distal Myopathy with Rimmed Vacuoles Presenting with Very Slow Progression

Abstract

We report novel compound heterozygous mutations of the UDP-N-acetylglucosamine-2-epimerase and N-acetylmannosamine kinase (GNE) gene, c.302G>A (p.R101H) and c.617-4A>G, in a Japanese family with distal myopathy with rimmed vacuoles (DMRV) presenting with slow progression. The three patients could stand and walk even 36, 34, and 39 years after onset, respectively, although affected individuals become wheelchair bound on average 12 years after onset of the disease. The clinical spectrum of DMRV seems to be wider than previously thought in terms of both the clinical course and the severity of the disease.

Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy)

“…Among five intronic mutations identified in our series, c.617−4A>G and c.769 + 4A>G were previously reported as pathological mutations 7 15. Three novel variants were located at splice junction of exon 6 (c.983–1delG), exon 8 (c.1411+5G>A) and exon 9 (c.1505–4G>A), raising the high possibility of relevant exons skipping.…”

Clinical and Electrophysiological Findings in Hereditary Inclusion Body Myopathy Compared With Sporadic Inclusion Body Myositis

“…26 Pure myopathic changes sparing the quadriceps were also described. 19,21,23 Neurogenic MUPs were reported in 2 additional GNEhIBM cases. 15 Overall, we did not find any difference between the 2 groups in the distribution of reinnervation (long-duration, high-amplitude) MUPs, CRDs, or frequency of myotonic discharges.…”

“…13 Reported description of the electromyographic (EMG) findings in genetically proven hIBM patients show some resemblance to those encountered in sIBM with essentially mixed myopathic and neurogenic features. 9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] In this study, we describe the clinical and electrophysiological features of hIBM subjects in comparison with their sIBM counterparts to identify differences that might help the clinical differential diagnosis.…”

Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy

“…FSHD (OMIM158900) is caused by a loss of the D4Z4 microsatellite locus on chromosome 4 [13] with a prevalence of approximately one per 20,000 Japanese [6]. DMRV (OMIM605820), also called Nonaka myopathy, hereditary inclusion body myopathy (hiBM), and quadriceps sparing myopathy, is an autosomal recessive vacuolar myopathy of the distal muscles of the tibialis anterior, caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase (GNE) gene [14]. The prevalence of DMRV is approximately 300-400 patients within the Japanese population.…”