論文

査読有り
2010年12月

STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern

EPILEPSIA
  • Hirotomo Saitsu
  • ,
  • Mitsuhiro Kato
  • ,
  • Ippei Okada
  • ,
  • Kenji E. Orii
  • ,
  • Tsukasa Higuchi
  • ,
  • Hideki Hoshino
  • ,
  • Masaya Kubota
  • ,
  • Hiroshi Arai
  • ,
  • Tetsuzo Tagawa
  • ,
  • Shigeru Kimura
  • ,
  • Akira Sudo
  • ,
  • Sahoko Miyama
  • ,
  • Yuichi Takami
  • ,
  • Toshihide Watanabe
  • ,
  • Akira Nishimura
  • ,
  • Kiyomi Nishiyama
  • ,
  • Noriko Miyake
  • ,
  • Takahito Wada
  • ,
  • Hitoshi Osaka
  • ,
  • Naomi Kondo
  • ,
  • Kiyoshi Hayasaka
  • ,
  • Naomichi Matsumoto

51
12
開始ページ
2397
終了ページ
2405
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/j.1528-1167.2010.02728.x
出版者・発行元
WILEY-BLACKWELL PUBLISHING, INC

P>Purpose:
De novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE). Our aim was to delineate the clinical spectrum of subjects with STXBP1 mutations, and to examine their biologic aspects.
Methods:
STXBP1 was analyzed in 29 and 54 cases of cryptogenic EIEE and West syndrome, respectively, as a second cohort. RNA splicing was analyzed in lymphoblastoid cells from a subject harboring a c.663 + 5G > A mutation. Expression of STXBP1 protein with missense mutations was examined in neuroblastoma2A cells.
Results:
A total of seven novel STXBP1 mutations were found in nine EIEE cases, but not in West syndrome. The mutations include two frameshift mutations, three nonsense mutations, a splicing mutation, and a recurrent missense mutation in three unrelated cases. Including our previous data, 10 of 14 individuals (71%) with STXBP1 aberrations had the onset of spasms after 1 month, suggesting relatively later onset of epileptic spasms. Nonsense-mediated mRNA decay associated with abnormal splicing was demonstrated. Transient expression revealed that STXBP1 proteins with missense mutations resulted in degradation in neuroblastoma2A cells.
Discussion:
Collectively, STXBP1 aberrations can account for about one-third individuals with EIEE (14 of 43). These genetic and biologic data clearly showed that haploinsufficiency of STXBP1 is the important cause for cryptogenic EIEE.

Web of Science ® 被引用回数 : 102

リンク情報
DOI
https://doi.org/10.1111/j.1528-1167.2010.02728.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000284849000006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/j.1528-1167.2010.02728.x
  • ISSN : 0013-9580
  • Web of Science ID : WOS:000284849000006

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