Identification of responsive genes for age-dependent infantile epileptic encephalopathy

2012 Fiscal Year Final Research Report

• Project/Area Number: 22689011
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Human genetics
• Research Institution: Yokohama City University
• Principal Investigator: SAITSU Hirotomo 横浜市立大学, 医学部, 医学部 (40402838)
• Project Period (FY): 2010 – 2012
• Keywords: ゲノムマイクロアレイ / 次世代シークエンサー / エクソーム解析 / 大田原症候群 / ウエスト症候群 / 早期発症てんかん性脳症

Research Abstract

We demonstrated that mutations in SPTAN1 cause West syndrome with myelination delay and atrophy of brain thought identification of a de novo microdeletion in a patient. We also clarified breakpoints of two balanced translocations, demonstrating involvement of abnormalities of SRGAP2 and MEF2C in epileptic encephalopathy. In addition, by whole exome sequencing, we identified mutations in KCNQ2 and CASK in patients with Ohtahara syndrome.

Research Products

• [Journal Article] Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly (2013)
  • Author(s): Yoneda Y, Haginoya K,…..*Saitsu H
  • Journal Title: Ann Neurol Volume: 73(1):48-57
  • DOI: DOI:10.1002/ana.23736
  • Peer Reviewed
• [Journal Article] Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome (2012)
  • Author(s): *Saitsu H et al.
  • Journal Title: Ann Neurol Volume: 72(2):298-300
  • DOI: DOI:10.1002/ana.23620
  • Peer Reviewed
• [Journal Article] CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia (2012)
  • Author(s): *Saitsu H et al.
  • Journal Title: Epilepsia Volume: 53(8):1441-1449
  • DOI: DOI:10.1111/j.1528-1167.2012.03548.x
  • Peer Reviewed
• [Journal Article] Progressive diffuse brain atrophy in West syndrome with marked hypomyelination due to SPTAN1 gene mutation (2012)
  • Author(s): Nonoda Y,…Saitsu H.
  • Journal Title: Brain Dev Volume: 31
  • DOI: DOI:10.1016/j.braindev.2012.05.002
  • Peer Reviewed
• [Journal Article] Early onset West syndrome with severe hypomyelination and coloboma-like optic discs in a girl with SPTAN1 mutation (2012)
  • Author(s): Writzl K,…Saitsu H.
  • Journal Title: Epilepsia Volume: 53(6):e106-10
  • DOI: DOI:10.1111/j.1528-1167.2012.03437.x
  • Peer Reviewed
• [Journal Article] Identification of a novel in-frame de novo mutation in SPTAN1 in intellectual disability and pontocerebellar atrophy (2012)
  • Author(s): Hamdan F, Saitsu H (Co-first Author) et al.
  • Journal Title: Eur J Hum Genet Volume: 20(7):796-800
  • DOI: DOI:10.1038/ejhg.2011.271
  • Peer Reviewed
• [Journal Article] Association of genomic deletions in the STXBP1 gene with Ohtahara syndrome (2012)
  • Author(s): *Saitsu H et al.
  • Journal Title: Clinical Genetics Volume: 81(4):399-402
  • DOI: DOI:10.1111/j.1399-0004.2011.01733.x
  • Peer Reviewed
• [Journal Article] De novo and inherited mutations in COL4A2, encoding the type IV collagen α2 chain cause porencephaly (2012)
  • Author(s): Yoneda Y,.…Saitsu H.
  • Journal Title: Am J Hum Genet Volume: 13;90(1):86-90
  • DOI: DOI:10.1016/j.ajhg.2011.11.016.
  • Peer Reviewed
• [Journal Article] A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5 (2012)
  • Author(s): *Saitsu H et al.
  • Journal Title: Brain Dev Volume: 34(5):364-7
  • DOI: DOI: 10.1016/j.braindev.2011.07.004
  • Peer Reviewed
• [Journal Article] De novo 5q14.3 translocation 121.5-kb upstream of MEF2C in a patient with severe intellectual disability and early-onset epileptic encephalopathy. (2011)
  • Author(s): *Saitsu H et al.
  • Journal Title: Am J Med Genet A Volume: 155A(11):2879-84
  • DOI: DOI:10.1002/ajmg.a.34289
  • Peer Reviewed
• [Journal Article] SMOC1 is essential for ocular and limb development in humans and mice (2011)
  • Author(s): Okada I, Hamanoue H,…*Saitsu H.
  • Journal Title: Am J Hum Genet Volume: 7;88(1):30-41
  • DOI: DOI: 10.1016/j.ajhg.2010.11.012
  • Peer Reviewed
• [Journal Article] Paternal mosaicism of a STXBP1 mutation in Ohtahara syndrome (2011)
  • Author(s): *Saitsu H et al.
  • Journal Title: Clinical Genetics Volume: 80(5):484-488
  • DOI: DOI:10.1111/j.1399-0004.2010.01575.x
  • Peer Reviewed
• [Journal Article] STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern (2010)
  • Author(s): *Saitsu H et al.
  • Journal Title: Epilepsia Volume: 51(12):2397-2405
  • DOI: DOI:10.1111/j.1528-1167.2010.02728.x
  • Peer Reviewed
• [Journal Article] Dominant negative mutations in α-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay (2010)
  • Author(s): *Saitsu H et al.
  • Journal Title: Am J Hum Genet Volume: 11;86(6):881-91
  • DOI: DOI:10.1016/j.ajhg.2010.04.013
  • Peer Reviewed
• [Journal Article] Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation
  • Author(s): Kato M, …Saitsu H.
  • Journal Title: Epilepsia
  • DOI: DOI:10.1111/epi.12200
  • Peer Reviewed
• [Journal Article] Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2)
  • Author(s): *Saitsu H et al.
  • Journal Title: Am J Med Genet A Volume: 158A(1):199-205
  • DOI: DOI:10.1002/ajmg.a.34363
  • Peer Reviewed
• [Journal Article] Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits Cause an Autosomal-Recessive Hypomyelinating Leukoencephalopathy
  • Author(s): *Saitsu H et al.
  • Journal Title: Am J Hum Genet Volume: 89(5): 644-51
  • DOI: DOI:10.1016/j.ajhg.2011.10.003
  • Peer Reviewed
• [Presentation] CASK aberrations in males with Ohtahara syndrome and cerebellar hypoplasia (2012)
  • Author(s): Saitsu H
  • Organizer: 62th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Moscone Center(San Francisco, USA)
  • Year and Date: 2012-11-09
• [Presentation] CASK の null 変異は小脳低形成を伴う大田原症候群をひきおこす (2012)
  • Author(s): 才津浩智
  • Organizer: 人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2012-10-25
• [Presentation] De novo and inherited mutations in COL4A2, encoding type IV collagen α2 chain cause porencephaly (2012)
  • Author(s): 才津浩智
  • Organizer: 第52回日本先天異常学会学術集会
  • Place of Presentation: 東京女子医科大学弥生記念講堂(東京都)
  • Year and Date: 2012-07-07
• [Presentation] Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an hypomyelinating leukoencephalopathy (2012)
  • Author(s): 才津浩智
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学(山梨県)
  • Year and Date: 2012-06-26
• [Presentation] 染色体異常をめぐって-ダウン症の病態解明- (2011)
  • Author(s): 才津浩智
  • Organizer: ダウン症候群の分子遺伝学的解析
  • Place of Presentation: シェーンバッハ砂防(東京都)
  • Year and Date: 2011-07-23
• [Presentation] α-II スペクトリンのドミナントネガティブ変異が髄鞘化障害を伴う West症候群を引き起こす (2011)
  • Author(s): 才津浩智
  • Organizer: 第51回日本先天異常学会学術集会
  • Place of Presentation: シェーンバッハ砂防(東京都)
  • Year and Date: 2011-07-22
• [Presentation] 年齢依存性てんかん性脳症の分子遺伝学的研究 (2010)
  • Author(s): 才津浩智
  • Organizer: 第55回日本人類遺伝学会(招待講演)
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
  • Year and Date: 2010-10-29
• [Presentation] 新規 CNV探索によるてんかん原因遺伝子の同定 (2010)
  • Author(s): 才津浩智
  • Organizer: 第18回精神行動遺伝医学会(招待講演)
  • Place of Presentation: 東北大学(宮城県)
  • Year and Date: 2010-09-18
• [Presentation] 先天異常疾患のゲノム遺伝子解析
  • Author(s): 才津浩智
  • Organizer: 第37回日本マス・スクリーニング学会(招待講演)
  • Place of Presentation: ワークピア横浜(神奈川)
• [Patent(Industrial Property Rights)] 孔脳症又は脳出血のリスクを予測する方法 (2011)
  • Inventor(s): 松本直通、才津浩智
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 特願 2011-247457
  • Filing Date: 2011-11-11
• [Patent(Industrial Property Rights)] び慢性大脳白質形成不全症患者又は保因者の検出方法 (2010)
  • Inventor(s): 松本直通、才津浩智
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 特願 2011-226488
  • Filing Date: 2010-10-14