Conprehensive analysis of SCN1A noncoding region for epileptic disorders

• Project/Area Number: 24791039
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: NAKAYAMA Tojo 東北大学, 大学病院, 助教 (40613302)
• Research Collaborator: KURE Shigeo 東北大学, 医学系研究科, 教授 (10205221) ; HIROSE Shinichi 福岡大学, 医学部, 教授 (60248515) ; YAMAMOTO Toshiyuki 東京女子医科大学, 医学部, 教授 (20252851)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: SCN1A遺伝子 / Dravet症候群 / 非翻訳領域 / 微小欠失 / 体細胞モザイク / SCN1A / プロモーター / 小児 / てんかん / 遺伝学的解析

Research Abstract

We investigated the noncoding regions of the SCN1A gene for 237 patients with Dravet syndrome and its related disorders who did not show any SCN1A mutations by sequence analysis of all coding exons and exon-intron boundaries. We invented Multiplex ligation-dependent probe amplification (MLPA) assays with probes for the 5'non-coding exons, their upstream and downstream regions of SCN1A. Among 237 patients, we found two patients with mosaic microdeletion removing the entire coding exons and boundary regions. We validated the mosaicism by subsequent array CGH and FISH. We also identified seven patients with deletions involving the coding region. One patient Dravet syndrome also showed a possible deletion in the 5'noncoding region which is detected by MLPA only. This study provides the first case of mosaic microdeletion involving the SCN1A region, and indicates the critical involvement of this mosaic microdeletion in the molecular pathology of Dravet syndrome.

Research Products

• [Journal Article] RBPJ is disrupted in a case of proximal 4p deletion syndrome with epilepsy (2013)
  • Author(s): Nakayama T, Saitsu H, Endo W, Kikuchi A, Uematsu M, Haginoya K, Hino-Fukuyo N, Kobayashi T, Iwasaki M, Tominaga T, Kure S, Matsumoto N
  • Journal Title: Brain Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] 総説 : てんかん症候群の疾患遺伝子up to date (2012)
  • Author(s): 中山東城, 福與なおみ, 植松貢, 呉繁夫
  • Journal Title: 日本小児科学会雑誌 Volume: 116巻9号 Pages: 1327-1336
• [Presentation] RBPJ 遺伝子異常を認めたてんかんを伴う近位4p 欠失症候群の一例 (2013)
  • Author(s): 中山東城, 才津浩智, 遠藤若葉, 菊池敦生, 植松貢, 萩野谷和裕, 福與なおみ, 小林朋子, 岩崎真樹, 冨永悌二, 呉繁夫, 松本直通
  • Organizer: 第57回日本人類遺伝学会
  • Place of Presentation: 仙台
  • Year and Date: 2013-10-22
• [Presentation] てんかんの遺伝学up to date ~原因遺伝子が近年同定されたてんかん症候群~ (2013)
  • Author(s): 中山東城
  • Organizer: 第7回日本てんかん学会関東甲信越地方会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-15
  • Invited
• [Book] 最近定義された遺伝子異常によるてんかん症候群, 日本てんかん学会編, てんかん専門医ガイドブック (2014)
  • Author(s): 中山東城
  • Publisher: 診断と治療社