TY - JOUR T1 - Mutation profile of the <em>GNE</em> gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy) JF - Journal of Neurology, Neurosurgery &amp; Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 914 LP - 917 DO - 10.1136/jnnp-2013-305587 VL - 85 IS - 8 AU - Anna Cho AU - Yukiko K Hayashi AU - Kazunari Monma AU - Yasushi Oya AU - Satoru Noguchi AU - Ikuya Nonaka AU - Ichizo Nishino Y1 - 2014/08/01 UR - http://jnnp.bmj.com/content/85/8/914.abstract N2 - Background GNE myopathy (also called distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy) is an autosomal recessive myopathy characterised by skeletal muscle atrophy and weakness that preferentially involve the distal muscles. It is caused by mutations in the gene encoding a key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). Methods We analysed the GNE gene in 212 Japanese GNE myopathy patients. A retrospective medical record review was carried out to explore genotype–phenotype correlation. Results Sixty-three different mutations including 25 novel mutations were identified: 50 missense mutations, 2 nonsense mutations, 1 insertion, 4 deletions, 5 intronic mutations and 1 single exon deletion. The most frequent mutation in the Japanese population is c.1714G&gt;C (p.Val572Leu), which accounts for 48.3% of total alleles. Homozygosity for this mutation results in more severe phenotypes with earlier onset and faster progression of the disease. In contrast, the second most common mutation, c.527A&gt;T (p.Asp176Val), seems to be a mild mutation as the onset of the disease is much later in the compound heterozygotes with this mutation and c.1714G&gt;C than the patients homozygous for c.1714G&gt;C. Although the allele frequency is 22.4%, there are only three homozygotes for c.527A&gt;T, raising a possibility that a significant number of c.527A&gt;T homozygotes may not develop an apparent disease. Conclusions Here, we report the mutation profile of the GNE gene in 212 Japanese GNE myopathy patients, which is the largest single-ethnic cohort for this ultra-orphan disease. We confirmed the clinical difference between mutation groups. However, we should note that the statistical summary cannot predict clinical course of every patient. ER -