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Neuromuscul Disord. 2018 Feb;28(2):154-157. doi: 10.1016/j.nmd.2017.11.003. Epub 2017 Nov 22.

GNE myopathy caused by a synonymous mutation leading to aberrant mRNA splicing.

Author information

1
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Department of Genome Medicine Development, Medical Genome Center (MGC), National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
2
Department of Neurology, Osaka University Graduate School of Medicine, D-4, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Neurology, Higashiosaka City Medical Center, 3-4-5 Nishi-iwata, Higashiosaka, Osaka, 578-8588, Japan.
3
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Department of Genome Medicine Development, Medical Genome Center (MGC), National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. Electronic address: satomi11@me.com.
4
Department of Neurology, Osaka University Graduate School of Medicine, D-4, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
5
Department of Neurology, Osaka University Graduate School of Medicine, D-4, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: mtakahas@sahs.med.osaka-u.ac.jp.
6
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Department of Genome Medicine Development, Medical Genome Center (MGC), National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.

Abstract

GNE myopathy is a rare autosomal recessive myopathy caused by bi-allelic mutations in GNE. We report the case of a 36-year-old man who presented with typical clinical and pathological features of GNE myopathy including distal dominant muscle weakness from the age of 29 and numerous rimmed vacuoles on muscle biopsy. Targeted next-generation sequencing revealed a novel synonymous mutation, c.1500A>G (p.G500=), together with a common Japanese mutation c.620A>T (p.D207V). The cDNA analysis of the biopsied muscle revealed that this synonymous mutation creates a cryptic splice donor site that causes aberrant splicing. This report will expand our understanding of the genetic heterogeneity of GNE myopathy emphasizing the importance of interpreting synonymous variants in genetic testing.

KEYWORDS:

Distal myopathy with rimmed vacuoles; Hereditary inclusion body myopathy; RNA; Splice

PMID:
29307446
DOI:
10.1016/j.nmd.2017.11.003

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