論文

査読有り
2017年2月

Gene dosage effect in spinocerebellar ataxia type 6 homozygotes: A clinical and neuropathological study

JOURNAL OF THE NEUROLOGICAL SCIENCES
  • Kazumasa Soga
  • ,
  • Kinya Ishikawa
  • ,
  • Tokuro Furuya
  • ,
  • Tadatsune Iida
  • ,
  • Tetsuo Yamada
  • ,
  • Noboru Ando
  • ,
  • Kiyobumi Ota
  • ,
  • Hiromi Kanno-Okada
  • ,
  • Shinya Tanaka
  • ,
  • Masayuki Shintaku
  • ,
  • Yoshinobu Eishi
  • ,
  • Hidehiro Mizusawa
  • ,
  • Takanori Yokota

373
開始ページ
321
終了ページ
328
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jns.2016.12.051
出版者・発行元
ELSEVIER SCIENCE BV

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disorder. However, it remains unclear whether SCA6 shows a gene dosage effect, defined by earlier age-of-onset in homozygotes than heterozygotes. Herein, we retrospectively analyzed four homozygous SCA6 subjects from our single institution cohort of 120 SCA6 subjects. We also performed a neuropathological investigation into an SCA6 individual with compound heterozygous expansions. In the 116 heterozygotes, there was an inverse correlation of age-of-onset with the number of CAG repeats in the expanded allele, and with the total number of CAG repeats, in both normal and expanded alleles. The age-of-onset in the four homozygotes was within the 95% confidence interval of the age-of onset versus the repeat-lengths correlations determined in the 116 heterozygotes. Nevertheless, all homozygotes had earlier onset than their parents, and showed rapid disease progression. Neuropathology revealed neuronal loss, as well as alpha 1A-calcium channel protein aggregates in Purkinje cells, a few alpha 1A-calcium channel protein aggregates in the neocortex and basal ganglia, and neuronal loss in Clarke's column and the globus pallidus not seen in heterozygotes. These data suggest a mild clinical and neuropathological gene dosage effect in SCA6 subjects. (C) 2016 Elsevier B.V. All rights reserved.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1016/j.jns.2016.12.051
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28131213
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000394200700072&DestApp=WOS_CPL

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