Genomic analysis identifies candidate pathogenic variants in trios with West syndrome by using array CGH

• Project/Area Number: 25461536
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Hino-Fukuyo Naomi 東北大学, 大学病院, 助教 (90400366)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ウエスト症候群 / infantile spasms / アレイCGH / トリオ検体 / 次世代シーケンサー / エクソーム解析 / de novo / トリオサンプル / アレイＣＧＨ

Outline of Final Research Achievements

West syndrome, which is narrowly defined as　infantile spasms that occur in clusters and hypsarrhythmia　on EEG, is the most common early-onset epileptic
encephalopathy (EOEE). The genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. The array CGH revealed candidate pathogenic copy number variations in two cases, including an Xq28 duplication and a 19p13.2 deletion. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases.There candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases.

Research Products

• [Journal Article] Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome. (2015)
  • Author(s): Hino-Fukuyo N, Kikuchi A, Arai-Ichinoi N, Niihori T, Sato R, Suzuki T, Kudo H, Sato Y, Nakayama T, Kakisaka Y, Kubota Y, Kobayashi T, Funayama R, Nakayama K, Uematsu M, Aoki Y, Haginoya K, Kure S.
  • Journal Title: Hum Genet. Volume: 134 Issue: 6 Pages: 649-658
  • DOI: 10.1007/s00439-015-1553-6
  • Peer Reviewed / Open Access
• [Journal Article] ビガバトリンを第一選択に用いた結節性硬化症を伴うウエスト症候群の1例 (2014)
  • Author(s): 佐藤優子、福與なおみら
  • Journal Title: 小児科臨床 Volume: 67 Pages: 1047-1050
  • Peer Reviewed
• [Presentation] 網羅的ゲノム解析によって候補遺伝子が明らかになった潜因性West症候群 (2015)
  • Author(s): 福與なおみ他
  • Organizer: 日本てんかん学会
  • Place of Presentation: 長崎（長崎ブリックホール）
  • Year and Date: 2015-10-30
• [Presentation] 潜因性West症候群の網羅的ゲノム解析ー18症例中9例で候補遺伝子を同定- (2015)
  • Author(s): 菊池敦生、福與なおみ他
  • Organizer: 第60回日本臨床遺伝学会
  • Place of Presentation: 東京（京王プラザホテル）
  • Year and Date: 2015-10-14
• [Presentation] 潜因性West症候群に対する 網羅的ゲノム解析による遺伝学的診断の有用性 (2015)
  • Author(s): 菊池敦生、福與なおみ他
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪（帝国ホテル大阪）
  • Year and Date: 2015-05-28