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

Wenhua Zhu; Masaki Eto; Satomi Mitsuhashi; Kazushiro Takata; Goichi Beck; Hisae Sumi-Akamaru; Hideki Mochizuki; Saburo Sakoda; Masanori P Takahashi; Ichizo Nishino

doi:10.1016/j.nmd.2017.11.003

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

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

Authors

Affiliations

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.

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

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Distal Myopathies / genetics*
Distal Myopathies / metabolism*
Distal Myopathies / pathology
Humans
Male
Multienzyme Complexes / genetics*
Multienzyme Complexes / metabolism*
Muscle, Skeletal / pathology
Mutation*
Phenotype
RNA Splicing* / genetics

Substances

Multienzyme Complexes
UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase

Supplementary concepts

Distal myopathy, Nonaka type