TDP-43 M337V Mutation in Familial Amyotrophic Lateral Sclerosis in Japan

• Tamaoka Akira

  Department of Neurology, Doctoral Program in Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Arai Makoto

  Tokyo Institute of Psychiatry

• Itokawa Masanari

  Tokyo Institute of Psychiatry

• Arai Tetsuaki

  Tokyo Institute of Psychiatry

• Hasegawa Masato

  Tokyo Institute of Psychiatry

• Tsuchiya Kuniaki

  Tokyo Metropolitan Matsuzawa Hospital

• Takuma Hiroshi

  Department of Neurology, Doctoral Program in Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Tsuji Hiroshi

  Department of Neurology, Doctoral Program in Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Ishii Akiko

  Department of Neurology, Doctoral Program in Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Watanabe Masahiko

  Department of Neurology, Doctoral Program in Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Takahashi Yuji

  Department of Neurology, Graduate School of Medicine, University of Tokyo

• Goto Jun

  Department of Neurology, Graduate School of Medicine, University of Tokyo

• Tsuji Shoji

  Department of Neurology, Graduate School of Medicine, University of Tokyo

• Akiyama Haruhiko

  Tokyo Institute of Psychiatry

Abstract

The clinical features of a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (ALS) are reported. Weakness initially affected the bulbar musculature, with later involvement of the extremities. Genetic studies failed to detect any mutations of the Cu/Zn superoxide dismutase-1 (SOD1) and Dynactin1 (DCTN1) genes, but revealed a single base pair change from wild-type adenine to guanine at position 1009 in TAR-DNA-binding protein (TDP-43), resulting in a methionine-to-valine substitution at position 337. The immunohistochemical study on autopsied brain of the proband's aunt showed TDP-43-positive cytoplasmic inclusions in the anterior horn cells of the spinal cord and in the hypoglossal nucleus, as well as glial cytoplasmic inclusions in the precentral gyrus, suggesting that a neuroglial proteinopathy was related to TDP-43. In conclusion, a characteristic clinical phenotype of familial ALS with initial bulbar symptoms occurred in this family with TDP-43 M337V substitution, the pathomechanism of which should be elucidated.<br>

Journal

• Internal Medicine

  Internal Medicine 49 (4), 331-334, 2010

  The Japanese Society of Internal Medicine

Keywords

• Amyotrophic lateral sclerosis (ALS)
• TAR-DNA-binding protein 43 (TDP-43)

Details

• CRID: 1390001204873164160
• NII Article ID: 130000152618
• DOI: 10.2169/internalmedicine.49.2915
• ISSN: 13497235
• ISSN: 09182918
• Web Site: http://www.jstage.jst.go.jp/article/internalmedicine/49/4/49_4_331/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010222784
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed