Identification of the new gene for familial parkinsonism and its functional analyses

• Project/Area Number: 20790625
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: FUNAYAMA Manabu Juntendo University, 大学院・医学研究科, 助教 (70468578)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: パーキンソン病 / 遺伝子 / SNPs / ゲノムワイド / 変異 / ハプロタイプ

Research Abstract

To confirm the pathogenesis of the novel candidate genes for autosomal recessive-late onset familial Parkinson disease (ARLOPD), I performed mutation screening in approximately 900 patients with Parkinson disease. Although I detected the heterozygous mutation in two patients, I still cannot conclude whether the gene is the definitive causal gene for ARLOPD. In addition, I found the new locus for ARLOPD. Further investigation is needed to identify the causal gene for ARLOPD.

Research Products

• [Journal Article] A rotarod test for evaluation of motor skill learning (2010)
  • Author(s): Shiotsuki H, Yoshimi K, Shimo Y, Funayama M, Takamatsu Y, Ikeda K, Takahashi R, Kitazawa S, Hattori N.
  • Journal Title: J Neurosci Methods.
  • Peer Reviewed
• [Journal Article] Rapid screening of ATP13A2 variant with high-resolution melting analysis. (2010)
  • Author(s): Funayama M
  • Journal Title: Movement Disorders. (In press)
  • Peer Reviewed
• [Journal Article] Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease: Large-scale collaborative study (2009)
  • Author(s): Evangelou E, Maraganore DM, Annesi G, et al.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 153B(1) Pages: 220-228
  • Peer Reviewed
• [Journal Article] Preserved cardiac 123I-MIBG uptake and lack of severe autonomic dysfunction in a PARK9 patient (2009)
  • Author(s): Kanai K, Asahina M, Arai K, Tomiyama H, Kuwabara Y, Uchiyama U, Sekiguchi Y, Funayama M, Kuwabara S, Hattori N, Hattori T.
  • Journal Title: Mov Disord 24(9) Pages: 1403-4
  • Peer Reviewed
• [Journal Article] A new mutation in the GCH1 gene presents as early-onset Parkinsonism (2009)
  • Author(s): Momma K, Funayama M, Li Y, Ichinose H, Motoyoshi K, Hattori N, Mizuno Y, Kamakura K.
  • Journal Title: Parkinsonism Relat Disord. 15(2) Pages: 160-1
  • Peer Reviewed
• [Journal Article] Screening PARK Genes for Mutations in Early Onset Parkinson ' s Disease Patients from Queensland, Australia. (2009)
  • Author(s): Mellick GD, Siebert GA, Funayama M, Buchanan DD, Li Y, Imamichi Y, Yoshino H, Silburn PA, Hattori N.
  • Journal Title: Parkinsonism Relat Disord 15(2) Pages: 105-9
  • Peer Reviewed
• [Journal Article] Screening PARK Genes for Mutations in Early Onset Parkinson's Disease Patients from Queensland, Australia. (2009)
  • Author(s): Mellick GD
  • Journal Title: Parkinsonism & Related Disorders 15(2) Pages: 105-109
  • Peer Reviewed
• [Journal Article] A new mutation in the GCH1 gene presents as early-onset Parkinsonism. (2009)
  • Author(s): Momma K
  • Journal Title: Parkinsonism & Related Disorders 15(2) Pages: 160-161
  • Peer Reviewed
• [Journal Article] Preserved cardiac <123>^I-MIBG uptake and lack of severe autonomic dysfunction in a PARK9 patient. (2009)
  • Author(s): Kanai K
  • Journal Title: Movement Disorders. 24(9) Pages: 1403-1404
  • Peer Reviewed
• [Journal Article] Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease : Large-scale collaborative study. (2009)
  • Author(s): Evangelou E
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. 153B(1) Pages: 220-228
  • Peer Reviewed
• [Journal Article] Mutation analyses in amyotrophic lateral sclerosis/parkinsonism-dementia complex of Kii, Japan (2008)
  • Author(s): Tomiyama H, Kokubo Y, Sasaki R, Li Y, Imamichi Y, Funayama M, Mizuno Y, Hattori N, Kuzuhara S.
  • Journal Title: Mov Disord. 23(16) Pages: 2344-8
  • Peer Reviewed
• [Journal Article] LRRK2 P755L variant in sporadic Parkinson's disease (2008)
  • Author(s): Tomiyama H, Mizuta I, Li Y, Funayama M, Yoshino H, Li L, Murata M, Yamamoto M, Kubo S, Mizuno Y, Toda T, Hattori N.
  • Journal Title: J Hum Genet. 53(11-12) Pages: 1012-5
  • NAID: 10025584966
  • Peer Reviewed
• [Journal Article] Familial parkinsonism with digenic parkin and PINK1 mutations (2008)
  • Author(s): Funayama M, Li Y, Tsoi TH, Lam CW, Ohi T, Yazawa S, Uyama E, Djaldetti R, Melamed E, Yoshino H, Imamichi Y, Takashima H, Nishioka K, Sato K, Tomiyama H, Kubo S, MD, Mizuno Y, Hattori N.
  • Journal Title: Mov Disord 65(6) Pages: 802-8
  • Peer Reviewed
• [Journal Article] Mutation analysis of the PINK1 gene in 391 patients with Parkinson's disease (2008)
  • Author(s): Kumazawa R, Tomiyama H, Li Y, Imamichi Y, Funayama M, Yoshino H, Yokochi F, Fukusako T, Takehisa Y, Kashihara K, Kondo T, Elibol B, Bostantjopoulou S, Toda T, Takahashi H, Yoshii F, Mizuno Y, Hattori N.
  • Journal Title: Arch Neurol 65(6) Pages: 802-8
  • Peer Reviewed
• [Journal Article] Analysis of Lrrk2 R1628P as a risk factor for Parkinson' s disease (2008)
  • Author(s): Ross OA, Wu YR, Lee MC, Funayama M, Chen ML, Soto AI, Mata IF, Lee-Chen GJ, Chen CM, Tang M, Zhao Y, Hattori N, Farrer MJ, Tan EK, Wu RM.
  • Journal Title: Ann Neurol. 64(1) Pages: 88-92
  • Peer Reviewed
• [Journal Article] PARK9-linked parkinsonism in Eastern Asia: Mutation detection in ATP13A2 and clinical phenotype (2008)
  • Author(s): Ning Y, Kanai K, Tomiyama H, Li Y, Funayama M, Yoshino H, Sato S, Asahina M, Kuwabara S, Takeda A, Hattori T, Mizuno Y, Hattori N
  • Journal Title: Neurology 70(162) Pages: 1491-1493
  • Peer Reviewed
• [Journal Article] Familial parkinsonism with digenic parkin and PINK1 mutations (2008)
  • Author(s): Funayama M, et.al.
  • Journal Title: MOVEMENT DISORDERS 65 Pages: 802-808
  • Peer Reviewed
• [Journal Article] Analysis of Lrrk2 R1628P as a risk factor for Parkinson' s disease (2008)
  • Author(s): Ross OA, et.al.
  • Journal Title: Annals of Neurology 64 Pages: 88-92
  • Peer Reviewed
• [Journal Article] LRRK2 P775L variant in sporadic Parkinson' s disease (2008)
  • Author(s): Tomiyama H, et.al.
  • Journal Title: Journal of Human Genetics 53 Pages: 1012-1015
  • Peer Reviewed
• [Journal Article] Rapid screening of ATP13A2 variant with high-resolution melting analysis
  • Author(s): Funayama M, Tomiyama H, Wu RM, Ogaki K, Yoshino H, Mizuno Y, Hattori N.
  • Journal Title: Mov Disord (in press)
  • Peer Reviewed
• [Presentation] 高分解能融解曲線分析法をもちいたATP13A2 A746T多型の大規模解析 (2009)
  • Author(s): 舩山学, 富山弘幸, 柳瀬貴章, Ruey-Meei Wu, 大垣光太郎, 吉野浩代, 水野美邦, 服部信孝
  • Organizer: 第3回パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 東京
  • Year and Date: 2009-10-10
• [Presentation] 高分解能融解曲線分析法をもちいたATP13A2 A746T多型の大規模解析. (2009)
  • Author(s): 舩山学
  • Organizer: 第3回パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 品川プリンスホテル(東京都)
  • Year and Date: 2009-10-10
• [Presentation] Hi-Res Melting法をもちいたATP13A2 A746T多型の高速解析 (2009)
  • Author(s): 舩山学, 富山弘幸, 柳瀬貴章, 吉野浩代, 水野美邦, 服部信孝
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-25
• [Presentation] Hi-Res Melting法をもちいたATP13A2 A746T多型の高速解析. (2009)
  • Author(s): 舩山学
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: グランドプリンスホテル高輪(東京都)
  • Year and Date: 2009-09-25
• [Presentation] Rapid screening of ATP13A2 variant with high-resolution melting analysis (2009)
  • Author(s): Funayama M, Tomiyama H, Wu RM, Yoshino H, Ogaki K, Mizuno Y, Hattori N.
  • Organizer: Genetic Epidemiology of Parkinson's Disease 4th annual meeting
  • Place of Presentation: Tubingen, Germany
  • Year and Date: 2009-07-08
• [Presentation] Rapid screening of ATP13A2 variant with high-resolution melting analysis. (2009)
  • Author(s): Funayama M
  • Organizer: Genetic Epidemiology of Parkinson's Disease 4th annual meeting.
  • Place of Presentation: Tubingen, Germany
  • Year and Date: 2009-07-08
• [Presentation] SNP chipによる家族性パーキンソン病のlinkage解析 (2009)
  • Author(s): 舩山学, 吉野浩代, 今道洋子, 李元 哲, 高嶋博, 松浦英治, 有村公良, 野元三治, 富山弘幸, 久保紳一郎, 水野美邦, 服部信孝
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-22
• [Presentation] SNP chipによる家族性パーキンソン病のlinkage解析. (2009)
  • Author(s): 舩山学
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 2009-05-22
• [Presentation] NDUFV2+/-マウスにおけるMPTP感受性の検討 (2008)
  • Author(s): 舩山学, 大橋聡, 市川直樹, 今井哲司, 山本庄司, 日下弘道, 板谷昌子, 平澤恵理, 水野美邦, 服部信孝
  • Organizer: 第8回日本ミトコンドリア学会年会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-20
• [Presentation] Autosomal recessive late onset parkinsonismの原因遺伝子探索 (2008)
  • Author(s): 舩山学, 吉野浩代, 今道洋子, 李元哲, 李林, 増田浩美, 板谷昌子, 高梨雅史, 高嶋博, 松浦英治, 有村公良, 野元三治, 富山弘幸, 久保紳一郎, 水野美邦, 服部信孝
  • Organizer: 第2回Movement Disorder Society, Japan学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-04
• [Presentation] NDUFV2+/-マウスにおけるMPTP感受性の検討 (2008)
  • Author(s): 舩山学, 大橋聡, 市川直樹, 今井哲司, 山本庄司, 日下弘道, 板谷昌子, 平澤恵理, 水野美邦, 服部信孝
  • Organizer: 生体機能と創薬シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-09-05
• [Presentation] Autosomal recessive late onset parkinsonismの原因遺伝子探索 (2008)
  • Author(s): 舩山学, 吉野浩代, 今道洋子, 李元哲, 李林, 増田浩美, 板谷昌子, 高梨雅史, 高嶋博, 松浦英治, 有村公良, 野元三治, 水野美邦, 服部信孝
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] Autosomal recessive late onset parkinsonismの原因遺伝子探索 (2008)
  • Author(s): 舩山学
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-05-16