Mutations associated with copy number variation in neurological disorders

• Project/Area Number: 21200041
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Neurology; 基礎ゲノム科学
• Research Institution: Niigata University
• Principal Investigator: IKEUCHI Takeshi 新潟大学, 研究推進機構, 准教授 (20372469)
• Co-Investigator(Renkei-kenkyūsha): KUWANO Ryozo 新潟大学, 脳研究所, 教授 (20111734)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥29,900,000 (Direct Cost: ¥23,000,000、Indirect Cost: ¥6,900,000); Fiscal Year 2011: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000); Fiscal Year 2010: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000); Fiscal Year 2009: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 神経疾患 / 遺伝子コピー数 / アルツハイマー病 / 遺伝性神経疾患 / 遺伝子同定 / ゲノムワイド解析 / 候補遺伝子アプローチ / 遺伝性精神疾患

Research Abstract

It has been demonstrated that a number of regions in human genome shows copy number variation. Some of them are apparently associated with disease conditions. In this study, we performed genome-wide survey to detect CNVs associated with disease condition using samples from familial cases with neurological disorders with unknown etiology. This analysis revealed that there are several regions with CNV in normal controls. In addition, we also found apparently pathogenic CNV in familial case with dementia.

Research Products

• [Journal Article] Autosomal dominant tauopathy with parkinsonism and central hypoventilation (2012)
  • Author(s): Omoto M, Suzuki S, Ikeuchi T, Ishihara T, Kobayashi T, Tsuboi Y, Ogasawara J, Koga M, Kawai M, Iwaki T, Kanda T
  • Journal Title: Neurology Volume: 78 Pages: 752-764
  • Peer Reviewed
• [Journal Article] Parkinsonian features in a patient with diffuse neurofibrillary tangles with calcification (DNTC) (2012)
  • Author(s): Ikeuchi T, Katsui T, Kasuga K, Hirose M, Nishizawa M
  • Journal Title: Parkinsonism & Related Disorders Volume: 18 Pages: 649-650
  • Peer Reviewed
• [Journal Article] Novel G37V mutation of SOD1 gene in autopsied patient with familial amyotrophic lateral sclerosis (2012)
  • Author(s): Kobayashi J, Kuroda M, Kawata A, Mochizuki Y, Mizutani T, Komori T, Ikeuchi T, Koide R
  • Journal Title: Amyotrophic Lateral Sclerosis Volume: 14 Pages: 570-572
  • Peer Reviewed
• [Journal Article] α-Synuclein as CSF and Blood Biomarker of Dementia with Lewy Bodies (2012)
  • Author(s): Kasuga K, Nishizawa M, Ikeuchi T
  • Journal Title: International Journal of Alzheimer's Disease Volume: 437025
  • Peer Reviewed
• [Journal Article] Cerebral small-vessel disease protein HTRA1 controls TGF-β1 signaling via cleavage of proTGF-β1 (2011)
  • Author(s): Shiga A, Nozaki H, Nihonmatsu M, Kawata H, Arima K, Ikeda S, Tanaka A, Nakano I, Ikeuchi T, Nishizawa M, Onodera O
  • Journal Title: Human Molecular Genetics Volume: 20 Pages: 1800-1810
  • Peer Reviewed
• [Journal Article] Predominant executive cognitive deficit and cerebral white matter lesion in a patient with fragile X-associated tremor/ataxia syndrome (FXTAS) (2011)
  • Author(s): Kasuga K, Ikeuchi T, Arakawa K, Yajima R, Tokugake T, Nishizawa M
  • Journal Title: Case Reports in Neurology Volume: 3 Pages: 118-123
  • Peer Reviewed
• [Journal Article] Genotype-phenotype correlations in early onset ataxia with ocular motor apraxia and hypoalbuminemia (2011)
  • Author(s): Yokoseki A, Ishihara T, Yamada M, Murakami C, Tsuchiya M, Date H, Sato T, Tada M, Ikeuchi T, Tsuji S, Nishizawa M, Onodera O
  • Journal Title: Brain Volume: 134 Pages: 1387-1399
  • Peer Reviewed
• [Journal Article] Clinical characteristics and evidence for a common founder in Japanese families with MAPT R406W mutation (2011)
  • Author(s): Ikeuchi T, Imamura T, Kawase Y, Kitade Y, Tokutake T, Yajima R, Tsukie T, Miyashita A, Sugishita M, Kuwano R, Nishizawa M
  • Journal Title: Dementia Geriatric Cognitive Disorders EXTRA Volume: 1 Pages: 267-275
  • Peer Reviewed
• [Journal Article] Predominant executive cognitive deficit and cerebral white matter lesionin a patient with fragile X-associated tremor/ataxia syndrome (FXTAS) (2011)
  • Author(s): Kasuga, et al.
  • Journal Title: Case Report in Neurology Volume: 3 Issue: 2 Pages: 118-123
  • DOI: 10.1159/000328838
  • Peer Reviewed
• [Journal Article] Evidence for a common founder and clinical characteristics of Japanese families with MAPT R406W mutation (2011)
  • Author(s): Ikeuchi, et al.
  • Journal Title: Dementia Geriatric Cognitive Disorder EXTRA Volume: 1 Issue: 1 Pages: 267-275
  • DOI: 10.1159/000331243
  • Peer Reviewed
• [Journal Article] Coordinated increase of y-secretase products in the plasma of some female Japanese sporadic Alzheimer's disease patients: quantitative analysis of p3-Alca with a new ELISA system (2011)
  • Author(s): Konno, et al.
  • Journal Title: Molecular Neurodegeneration Volume: 6 Issue: 1 Pages: 76-76
  • DOI: 10.1186/1750-1326-6-76
  • Peer Reviewed
• [Journal Article] Involvement of Onuf's nucleus in Machado-Joseph disease (2010)
  • Author(s): Shimizu H, Yamada M, Toyoshima Y, Ikeuchi T, Onodera O, Takahashi H
  • Journal Title: Acta Neuropathologica Volume: 120 Pages: 439-448
  • Peer Reviewed
• [Journal Article] Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy (DRPLA): a correlation with CAG repeat length (2010)
  • Author(s): Hasegawa A, Ikeuchi T, Koike R, Mataubara N, Tsuchiya M, Nozaki H, Homma A, Idezuka J, Nishizawa M, Onodera O
  • Journal Title: Movement Disorders Volume: 25 Pages: 1694-1700
  • Peer Reviewed
• [Journal Article] Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, parkinsonism and motor neuron disease: a distinct clinicopathological and biochemical disease entity (2010)
  • Author(s): Fu Y, Nishihira Y, Kuroda S, Toyoshima Y, Ishihara T, Shinozaki M, Miyashita A, Piao YS, Tan CF, Tani T, Koide R, Iwanaga K, Tsujihata M, Onodera O, Kuwano R, Nishizawa M, Kakita A, Ikeuchi T, Takahashi H
  • Journal Title: Acta Neuropathologica Volume: 120 Pages: 21-32
  • Peer Reviewed
• [Journal Article] Alzheimer's disease: Report of two autopsy cases with a clinical diagnosis of corticobasal degeneration (2010)
  • Author(s): Okazaki K, Fu Y-J, Nishihira Y, Endo M, Fukushima T, Ikeuchi T, Okamoto K, Onodera O, Nishizawa M, Takahashi H
  • Journal Title: Neuropathology Volume: 30 Pages: 140-148
  • NAID: 10029320298
  • Peer Reviewed
• [Journal Article] Differential levels of α-synuclein, β-amyloid, and tau in cerebrospinal fluid between patients with dementia with Lewy bodies and Alzheimer disease (2010)
  • Author(s): Kasuga K, Tokutake T, Ishikawa A, Uchiyama T, Tokuda T, Onodera O, Nishizawa M, Ikeuchi T
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 81 Pages: 608-610
  • Peer Reviewed
• [Journal Article] Increased levels of soluble LR11 in cerebrospinal fluid of patients with Alzheimer disease (2010)
  • Author(s): Ikeuchi, et al
  • Journal Title: Dementia and Geriatric Cognitive Disorders Volume: 30 Pages: 28-32
  • Peer Reviewed
• [Journal Article] Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy (DRPLA) : a correlation with CAG repeat length (2010)
  • Author(s): Hasegawa, et al
  • Journal Title: Movement Disorders Volume: 25 Pages: 1694-1700
  • Peer Reviewed
• [Journal Article] Differential levels of α-synuclein, β-amyloid, and tau in cerebrospinal fluid between patients with dementia with Lewy bodies and Alzheimer disease (2010)
  • Author(s): Kasuga, et al
  • Journal Title: Journal of Neurology, Neurosurgery, Psychiatry Volume: 81 Pages: 608-610
  • Peer Reviewed
• [Journal Article] Depression and psychiatric symptoms preceding onset of dementia in family with early-onset Alzheimer disease with novel PSEN1 mutation (2009)
  • Author(s): Kasuga, et al.
  • Journal Title: Journal of Neurology Volume: 256 Pages: 1351-1353
  • Peer Reviewed
• [Journal Article] Mutations in HTRA1 are associated with familial ischemic cerebral small-vessel disease. (2009)
  • Author(s): Hara, et al.
  • Journal Title: New England Journal of Medicine Volume: 360 Pages: 1729-1739
  • Peer Reviewed
• [Journal Article] Novel GFAP mutation in patient with adult-onset Alexander disease presenting with spastic ataxia (2009)
  • Author(s): Kaneko, et al.
  • Journal Title: Movement Disorders Volume: 24 Pages: 1393-1395
  • Peer Reviewed
• [Journal Article] Kuwano R. SORL1 is genetically associated with late-onset al.zheimer's disease in Japanese, Koreans and Caucasian
  • Author(s): Miyashita A, Koike A, Jun G, (13名略), Ikeuchi T, (42名略)
  • Journal Title: PLOS One Volume: (in press)
  • Peer Reviewed
• [Journal Article] Extensive aggregation of α-synuclein and tau in juvenile-onset neuroaxonal dystrophy: an autopsied individual with a novel mutation in the PLA2G6 gene-splicing site
  • Author(s): Riku Y, Ikeuchi T, Yoshino H, Mimuro M, Mano K, Goto Y, Hattori N, Sobue G, Yoshida M
  • Journal Title: Acta Neuropathologica Communication Volume: (in press)
  • Peer Reviewed
• [Presentation] 神経軸索スフェロイドを伴う白質脳症HDLSの臨床・遺伝学的解析 (2013)
  • Author(s): 他田正義,今野卓哉,他田真理,荒川武蔵,小山哲秀,野崎洋明,針谷康夫,西宮仁,松永晶子,米田誠,吉倉延亮,犬塚貴,石原健司,河村満,高橋均,小野寺理,西澤正豊,池内 健
  • Organizer: 第54回日本神経学会
  • Place of Presentation: 東京
  • Year and Date: 2013-05-31
• [Presentation] 神経軸索スフェロイドを伴う白質脳症HDLSにおけるCSF-1Rシグナル伝達異常の解析 (2013)
  • Author(s): 今野卓哉,他田正義,小山哲秀,他田真理,荒川武蔵,野崎洋明,針谷康夫,西宮仁,松永晶子,米田誠,吉倉延亮,犬塚貴,石原健司,河村満,高橋均,小野寺理,西澤正豊,池内 健
  • Organizer: 第54回日本神経学会
  • Place of Presentation: 東京
  • Year and Date: 2013-05-31
• [Presentation] リポタンパク受容体LR11によるアポリポ蛋白E(ApoE)アイソフォーム依存性の調節機構 (2012)
  • Author(s): 西野香織,矢島隆二,徳武孝允,手塚敏之,西澤正豊,池内 健
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] 若年性認知症を呈する白質脳症:HDLS患者のCSF1R変異,MRI所見,臨床像,病理像の検討 (2012)
  • Author(s): 今野卓哉,他田正義,小山哲秀,荒川武蔵,岡崎健一,柿田明美,高橋均,西澤正豊,小野寺理,池内 健
  • Organizer: 第31回日本認知症学会
  • Place of Presentation: つくば市
  • Year and Date: 2012-10-26
• [Presentation] 脳アミロイドアンギオパチー関連炎症の臨床的多様性:画像所見,APOE,血中Aβ抗体 (2012)
  • Author(s): 須貝章弘,石井賢二,赤岩靖久,本間篤,藤田信也,田中晋,豊原潤,石渡喜一,西澤正豊,池内 健
  • Organizer: 第31回日本認知症学会
  • Place of Presentation: つくば市
  • Year and Date: 2012-10-26
• [Presentation] Late Breaking Symposium「新たな若年性認知症:神経軸索ジストロフィーを伴う遺伝性白質脳症(HDLS).HDLSの分子病態と白質を主病変とする他疾患との異常 (2012)
  • Author(s): 池内 健
  • Organizer: 第53回 日本神経学会学術大会.
  • Place of Presentation: 東京
  • Year and Date: 2012-05-25
• [Presentation] アルツハイマー病の発症機構における糖尿病の関与 (2011)
  • Author(s): 池内健
  • Organizer: 第30回日本認知症学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] アルツハイマー病患者・髄液中における可溶性LR11の増加 (2011)
  • Author(s): 池内 健,平山哲,三井田孝,深町勇,矢島隆二,徳武孝允,金子博之,春日健作,海老沼宏幸,田久保耕平,武城英明,西澤正豊
  • Organizer: 第52回日本神経学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-20
• [Presentation] βアミロイドによる誘発されるタウリン酸化におけるインスリンシグナル障害の関与 (2011)
  • Author(s): 徳武孝允,池内 健,春日健作,矢島隆二,石原智彦,西澤正豊
  • Organizer: 第52回日本神経学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-19
• [Presentation] レビー小体型認知症(DLB)の新規バイオマーカー:髄液αシヌクレインのELISA定量 (2010)
  • Author(s): 徳武孝允,春日健作,矢島隆二,石川厚,内山剛,徳田隆彦,西澤正豊,池内 健
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-05
• [Presentation] アルツハイマー病患者・髄液中では可溶性LR11が増加する (2010)
  • Author(s): 池内 健,平山哲,三井田孝,深町勇,矢島隆二,徳武孝允,春日健作,金子博之,田久保耕平,海老沼宏幸,武城英明,西澤正豊
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-05
• [Presentation] アルツハイマー病患者・髄液中では可溶型LR11が増加する (2010)
  • Author(s): 池内健, 他
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-11-05
• [Presentation] 健忘主体の臨床徴候を呈するタウ遺伝子R406W変異を伴う家族性認知症 (2010)
  • Author(s): 池内 健,春日健作,宮下哲典,川瀬康裕,杉下守弘,桑野良三,西澤正豊
  • Organizer: 第51回日本神経学会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-20
• [Presentation] βアミロイド依存性タウリン酸化カスケードにおけるインスリンシグナル障害の関与 (2010)
  • Author(s): 徳武孝允,池内 健,春日健作,篠崎 真,小野寺理,西澤正豊
  • Organizer: 第51回日本神経学会 2
  • Place of Presentation: 東京
  • Year and Date: 2010-05-20
• [Presentation] 健忘主体な特異な臨床型を呈したタウ遺伝子(MAPT)R406W変異を伴う家族性認知症の臨床分子遺伝学的解析 (2009)
  • Author(s): 池内健, 他
  • Organizer: 第28回日本認知症学会学術集会
  • Place of Presentation: 東北大学百周年記念会館(宮城県)
  • Year and Date: 2009-11-21
• [Book] 認知症診療Q&A (2012)
  • Author(s): 池内 健,他
  • Publisher: 中外医学社
• [Book] 日本臨床,認知症学 (上) (2011)
  • Author(s): 池内 健,他
  • Total Pages: 103
  • Publisher: Progranulin
• [Book] 綜合臨牀認知症の疫学・遺伝学 (2011)
  • Author(s): 池内 健
  • Total Pages: 1809
• [Book] 最新医学生化学マーカー,遺伝子 (2011)
  • Author(s): 池内 健,他
  • Total Pages: 2122