Brief Clinical Note : A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement

• Kawakami Nobuko

  Department of Neurology, Shizuoka General Hospital Department of Neurology, Kyoto University Graduate School of Medicine

• Komatsu Kenichi

  Department of Neurology, Kyoto University Graduate School of Medicine Department of Neurology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute

• Yamashita Hirofumi

  Department of Neurology, Kyoto University Graduate School of Medicine

• Uemura Kengo

  Department of Neurology, Kyoto University Graduate School of Medicine Ishiki Hospital

• Oka Nobuyuki

  Department of Neurology, Kyoto University Graduate School of Medicine Department of Neurology, National Hospital Organization Minami Kyoto Hospital

• Takashima Hiroshi

  Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences

• Takahashi Ryosuke

  Department of Neurology, Kyoto University Graduate School of Medicine

書誌事項

タイトル別名

• A novel mutation in <i>glycyl-tRNA synthetase</i> caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement
• A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement

抄録

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy; symptoms include distal wasting and weakness, usually with some sensory impairment. The clinical course is typically benign and the disease is not life threatening; however, in some cases, severe phenotypes include serious respiratory distress. CASE REPORT: Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). This mutation was considered pathogenic based on molecular evidence; notably, it was unique in that all other reported GARS mutations associated with severe phenotypes are located in an anticodon-binding domain, while in this case in an apparently non-functional region of the GARS gene. Not a simple loss-of-function mechanism, but rather gain-of-function mechanisms have also been reported in GARS mutations. This case provided useful information for understanding the mechanism of CMT2D/dSMA-V.

収録刊行物

• 臨床神経学

  臨床神経学 54 (11), 911-915, 2014

  日本神経学会

キーワード

• Charcot-Marie-Tooth disease
• hereditary sensory and motor neuropathy
• glycine-tRNA ligase
• spinal muscular atrophy
• respiratory distress

詳細情報

• CRID: 1390001205037344768
• NII論文ID: 130004706051
• NII書誌ID: AN00253207
• DOI: 10.5692/clinicalneurol.54.911
• ISSN: 18820654
• ISSN: 0009918X
• NDL書誌ID: 025922827
• PubMed: 25420567
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025922827
• Web Site: https://search.jamas.or.jp/link/ui/2015177019
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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