The detection of modifier gens in alpha-synuclein multiplications

• Project/Area Number: 25860726
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Nishioka Kenya 順天堂大学, 医学部, 准教授 (40348933)
• Research Collaborator: HATTORI Nobutaka 順天堂大学, 医学部, 教授 (80218510) ; MANABU Funayama 順天堂大学, 医学部, 准教授 (70468578) ; LI Yuanzhe 順天堂大学, 医学部 (40549292) ; TODA Tatsushi 神戸大学, 医学部, 教授 (30262025) ; Farrer Matthew J University of British Columbia, Department of Medical Genetics ; Ross Owen A. Mayo Clinic, Associate Professor of Neuroscience ; Kruger Rejko Kruger University of Luxembourg, Clinical&Experimental Neuroscience group
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: パーキンソン病 / alpha-synuclein / SNCA / 遺伝子重複 / びまん性レビー小体病 / 認知症 / 遺伝子 / DNA / 二倍体 / Gene chip / duplication / 変異 / 重複 / SNCS

Outline of Final Research Achievements

We enrolled 20 patients harboring SNCA duplication (Male:Female=8:12) derived from six Japanese families. We divided them to two groups of symptomatic carriers and asymptomatic carriers. Genes were analyzed by genechip of Affymetrix and searched all SNPs in exons. We estimated the region having over 3.0 of LOD score, including 18 novel genes. Eventually, we have difficulty to detect the precise candidate genes in this study. We have started to analyze data again adding the 50 samples harboring SNCA duplication, derived from around world, collaborating with University of British Columbia.

Research Products

• [Journal Article] A novel mutation of CHCHD2 p.R8H in a sporadic case of Parkinson's disease (2017)
  • Author(s): Ikeda, Aya; Matsushima, Takashi; Daida, Kensuke; Nakajima, Sho; Conedera, Silvio; Li, Yuanzhe; Yoshino, Hiroyo; Oyama, Genko; Funayama, Manabu; Nishioka, Kenya; Hattori, Nobutaka
  • Journal Title: PARKINSONISM & RELATED DISORDERS Volume: 34 Pages: 66-68
  • DOI: 10.1016/j.parkreldis.2016.10.018
  • Peer Reviewed
• [Journal Article] Genotype-phenotype correlations of cysteine replacement in CADASIL (2017)
  • Author(s): Matsushima, Takashi; Conedera, Silvio; Tanaka, Ryota; Li, Yuanzhe; Yoshino, Hiroyo; Funayama, Manabu; Ikeda, Aya; Hosaka, Yuka; Okuzumi, Ayame; Shimada, Yoshiaki; Yamashiro, Kazuo; Motoi, Yumiko; Nishioka, Kenya; Hattori, Nobutaka
  • Journal Title: NEUROBIOLOGY OF AGING Volume: 50 Pages: 169.e7-169.e14
  • DOI: 10.1016/j.neurobiolaging.2016.10.026
  • Peer Reviewed
• [Journal Article] FBXO7 mutations in Parkinson's disease and multiple system atrophy. (2016)
  • Author(s): Conedera S, Apaydin H, Li Y, et al.
  • Journal Title: Neurobiol Aging. Volume: 40 Pages: 192.e1-192.e5
  • DOI: 10.1016/j.neurobiolaging.2016.01.003
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic Association between Presenilin 2 Polymorphisms and Alzheimer's Disease and Dementia of Lewy Body Type in a Japanese Population. (2016)
  • Author(s): Suzuki A, Shibata N, Kasanuki K, et al.
  • Journal Title: Dement Geriatr Cogn Dis Extra. Volume: 16 Issue: 1 Pages: 90-97
  • DOI: 10.1159/000444080
  • Peer Reviewed
• [Journal Article] Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication. (2016)
  • Author(s): Takamura S, Ikeda A, Nishioka K, Furuya H, Tashiro M, Matsushima T, Li Y, Yoshino H, Funayama M, Morinobu S, Hattori N.
  • Journal Title: Parkinsonism Relat Disord. Volume: S1353-8020 Pages: 30028-1
  • DOI: 10.1016/j.parkreldis.2016.01.028
  • Peer Reviewed / Open Access
• [Journal Article] Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study. (2016)
  • Author(s): Takeshita Y, Shibata N, Kasanuki K, Nagata T, Shinagawa S, Kobayashi N, Ohnuma T, Suzuki A, Kawai E, Takayama T, Nishioka K, Motoi Y, Hattori N, Nakayama K, Yamada H, Arai H.
  • Journal Title: International Journal of Geriatric Psychiatry Volume: 4 Issue: 12 Pages: 1241-1246
  • DOI: 10.1002/gps.4600
  • Peer Reviewed
• [Journal Article] Anterior opercular syndrome induced by Epstein-Barr virus encephalitis. (2016)
  • Author(s): Matsushima T, Nishioka K, Tanaka R, et al.
  • Journal Title: Neurocase. Volume: 22 Issue: 1 Pages: 103-108
  • DOI: 10.1080/13554794.2015.1051054
  • Peer Reviewed
• [Journal Article] Fibromyalgia syndrome and cognitive dysfunction in elderly: a case series. (2016)
  • Author(s): Nishioka K, Hayashi T, Suzuki M, et al.
  • Journal Title: Int J Rheum Dis. Volume: 19 Issue: 1 Pages: 21-29
  • DOI: 10.1111/1756-185x.12734
  • Peer Reviewed
• [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study. (2015)
  • Author(s): Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
  • Journal Title: Lancet Neurol Volume: 14 Issue: 3 Pages: 274-282
  • DOI: 10.1016/s1474-4422(14)70266-2
  • Peer Reviewed / Open Access
• [Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β. (2015)
  • Author(s): Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara K, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
  • Journal Title: EMBO J. Volume: 34 Issue: 8 Pages: 1042-55
  • DOI: 10.15252/embj.201489897
  • Peer Reviewed / Open Access
• [Journal Article] High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism. (2015)
  • Author(s): Nishioka K, Oyama G, Yoshino H, Li Y, Matsushima T, Takeuchi C, Mochizuki Y, Mori-Yoshimura M, Murata M, Yamasita C, Nakamura N, Konishi Y, Ohi K, Ichikawa K, Terada T, Obi T, Funayama M, Saiki S, Hattori N.
  • Journal Title: Neurobiol Aging. Volume: S0197 Issue: 5 Pages: 54-58
  • DOI: 10.1016/j.neurobiolaging.2015.01.020
  • Peer Reviewed
• [Journal Article] ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout. (2015)
  • Author(s): Matsuo H, Tomiyama H, Satake W, Chiba T, Onoue H, Kawamura Y, Nakayama A, ShimizuS, Sakiyama M, Funayama M, Nishioka K, Shimizu T, Kaida K, Kamakura K, Toda T, Hattori N, ShinomiyaN.
  • Journal Title: Ann Clin Transl Neurol Volume: 2 Issue: 3 Pages: 302-306
  • DOI: 10.1002/acn3.167
  • Peer Reviewed / Open Access
• [Journal Article] Psychometric assessment of the Japanese version of the Revised Fibromyalgia Impact Questionnaire: reliability and validity. (2015)
  • Author(s): Isomura T, Nakamura I, Kawaguchi M, et al.
  • Journal Title: Int J Rheum Dis. Volume: 4 Issue: 9 Pages: 1088-1094
  • DOI: 10.1111/1756-185x.12574
  • Peer Reviewed
• [Journal Article] Beneficial Therapeutic Effects of Spinal Cord Stimulation in Advanced Cases of Parkinson's Disease With Intractable Chronic Pain: A Case Series. (2015)
  • Author(s): Nishioka K, Nakajima M.
  • Journal Title: Neuromodulation. Volume: 18 Issue: 8 Pages: 751-753
  • DOI: 10.1111/ner.12315
  • Peer Reviewed
• [Journal Article] The prevalence and risk factors of cerebral microbleeds in patients with Parkinson's disease. (2015)
  • Author(s): Yamashiro K, Tanaka R, Hoshino Y, et al.
  • Journal Title: Parkinsonism Relat Disord. Volume: 21 Issue: 9 Pages: 1076-1081
  • DOI: 10.1016/j.parkreldis.2015.06.019
  • Peer Reviewed
• [Journal Article] Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders. (2015)
  • Author(s): Ogaki K, Koga S, Heckman MG, et al.
  • Journal Title: Neurology Volume: 85 Issue: 23 Pages: 2016-2025
  • DOI: 10.1212/wnl.0000000000002170
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Beneficial therapeutic effects of spinal cord stimulation in advanced cases of Parkinson’s disease with intractable chronic pain: results of a case series (2015)
  • Author(s): Nishioka K. Nakajima M.
  • Journal Title: Neuromodulation Volume: in press
  • Peer Reviewed
• [Journal Article] Anterior opercular syndrome induced by Epstein-Barr virus encephalitis. (2015)
  • Author(s): Matsushima T, Nishioka K, Tanaka R, Yokoyama K, Hattori N.
  • Journal Title: Neurocase Volume: in press
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of electroconvulsive therapy for Parkinson’s disease with refractory psychiatric symptoms. (2014)
  • Author(s): Nishioka K, Tanaka R, Shimura H, Hirano K, Hatano T, Miyakawa K, Arai H, Hattori N, Urabe T.
  • Journal Title: Journal of Neural Transmission Volume: 121 Issue: 11 Pages: 1405-1410
  • DOI: 10.1007/s00702-014-1212-4
  • Peer Reviewed
• [Journal Article] EIF4G1 gene mutations are not a common cause of Parkinson's disease in the Japanese population (2014)
  • Author(s): Nishioka K, Funayama M, Vilarino-GuellC, Ogaki K, Li Y, Sasaki R, Kokubo Y, Kuzuhara S, Kachergus JM, Cobb SA, Takahashi H, Mizuno Y, Farrer MJ, Ross OA, Hattori N
  • Journal Title: Parkinsonism Relat Disord. Volume: 20 Issue: 6 Pages: 659-61
  • DOI: 10.1016/j.parkreldis.2014.03.004
  • Peer Reviewed
• [Journal Article] An epidemiologic internet survey of fibromyalgia and chronic pain in Japan. (2014)
  • Author(s): Nakamura I, Nishioka K, Usui C, Osada K, Ichibayashi H, Ishida M, Turk DC, Matsumoto Y, Nishioka K.
  • Journal Title: Arthritis Care and Research Volume: 66(7) Issue: 7 Pages: 1093-1101
  • DOI: 10.1002/acr.22277
  • Peer Reviewed
• [Journal Article] Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease. (2014)
  • Author(s): Li Y, Sekine T, Funayama M, Li L, Yoshino H, Nishioka K, Tomiyama H, Hattori N
  • Journal Title: Neurobiol Aging. Volume: 35 Issue: 4 Pages: 935.e3-935.e8
  • DOI: 10.1016/j.neurobiolaging.2013.09.019
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of electroconvulsive therapy for Parkinson's disease with refractory psychiatric symptoms. (2014)
  • Author(s): Nishioka K et al.
  • Journal Title: Journal of neural transmissoin Volume: in press
  • Peer Reviewed
• [Journal Article] Cerebral dural sinus thrombosis associated with adenomyosis: a case report. (2014)
  • Author(s): Nishioka K et al.
  • Journal Title: Journal of stroke and cerebrovascular diseases Volume: in press
  • Peer Reviewed
• [Presentation] Analysis of GCH1 mutations in the patients with Parkinson’s disease in Japanese population (2016)
  • Author(s): Kenya Nishioka, Hiroyo Yoshino, Takashi Matsushima, Aya Ikeda, Manabu Funayama, Nobutaka Hattori
  • Organizer: 11th Annual Meeting of the Genetic Epidemiology of Parkinson’s disease (GEOPD) Consortium
  • Place of Presentation: Campus Belval, Luxembourg
  • Year and Date: 2016-10-06
  • Int'l Joint Research
• [Presentation] Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication (2016)
  • Author(s): Silvio Conedera, Aya Ikeda, Kenya Nishioka, Shogo Takamura, Takashi Matsushima, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Shigeru Morinobu, Nobutaka Hattori
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2016-05-18
• [Presentation] Analysis of GCH1 mutations in the patients with Parkinson’s disease in Japanese population (2016)
  • Author(s): Hiroyo Yoshino, Kenya Nishioka, Aya Ikeda, Takashi Matsushima, Mitsuaki Oki, Daigo Miyazaki, Yoshiki Sekijima, Ai Hosaka, Takekazu Ohi, Hiroshi Iwanaga, Yuanzhe Li, Manabu Funayama, Nobutaka Hattori
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2016-05-18
• [Presentation] The analyze of four pedigrees with MAPT N279K mutation accompanying DAT scan and Tau imaging (2016)
  • Author(s): Aya Ikeda (Manabe), Kenya Nishioka, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Takashi Matsushima, Shinichi Ueno, Naohide Kurita, Hitoshi Shimada, Naruhiko Sahara, Makoto Higuchi, Tetsuya Suhara, Yuji Ueno, Masashi Takanashi, Yumiko Motoi, Nobutaka Hattori
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2016-05-18
• [Presentation] The comprehensive study of four pedigrees harboring MAPT N279K; genetics, pathology, and neuroimaging; DAT-scan and [¹¹C]PBB3 PET. (2015)
  • Author(s): Kenya Nishioka, Aya Ikeda, Li Yuanzhe, et al.
  • Organizer: GEOPD
  • Place of Presentation: 東京
  • Year and Date: 2015-10-01
  • Int'l Joint Research
• [Presentation] The Comprehensive study of genetics of Parkinson’s disease (2015)
  • Author(s): Kenya Nishioka, Hiroyo Yoshino, Yuanzher Li et al.
  • Organizer: 56th Annual Meeting of the Japanese Society of Neurology
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] 教育講演ベーシック明日からの臨床に役立つパーキンソン病診断 up to date (2015)
  • Author(s): 西岡健弥 服部信孝
  • Organizer: 第５６回 日本神経学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] High frequency of WDR45 mutation in Japanese patients with beta- propeller protein-associated neurodegeneration (BPAN) (2014)
  • Author(s): Nishioka K, Oyama G, Yoshino H, Li Y, Matsushima T, Takeuchi C, Mochizuki Y, Mori-Yoshimura M, Murata M, Yamasita C, Nakamura N, Konishi Y, Ohi K, Ichikawa K, Terada T, Obi T, Funayama M, Saiki S, Hattori N.
  • Organizer: 9th Annual Genetics Epidemiology of Parkinson's Disease Consortium
  • Place of Presentation: Vancouver, British Columbia
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] 精神発達遅滞と片側パーキンソニズムを呈しWDR45遺伝子変異を認めたNBIAの36歳女性例 (2014)
  • Author(s): 中里朋子、大山彦光、西岡健弥、吉野浩代、服部信孝
  • Organizer: 日本神経学会関東地方会
  • Place of Presentation: 砂防会館
  • Year and Date: 2014-05-31
• [Presentation] 首下がり症候群 パーキンソン病と多系統萎縮症を対象とした後ろ向き解析 (2014)
  • Author(s): 中村亮太、西岡健弥、山城一雄、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] GBA遺伝子変異を伴う家族性パーキンソン病の臨床遺伝学的検討 (2014)
  • Author(s): 李元哲、舩山学、李林、吉野浩代、西岡健弥、富山弘幸、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 異染性白質ジストロフィー患者の家族に発症したパーキンソン病２症例の検討 (2014)
  • Author(s): 金井数明、李元哲、中谷光良、藤巻基紀、舩山学、西岡健弥、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 認知症と全身に広がる慢性疼痛を合併した症例の解析 (2014)
  • Author(s): 林徹生、西岡健弥、鈴木通真、李元哲、本井ゆみ子、井関雅子、西岡久寿樹、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 進行性失語症のバイオロジカルマーカーに基づいた臨床解析 (2014)
  • Author(s): 城崇之、西岡健弥、原裕子、本井ゆみ子、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 日本人パーキンソン病患者におけるαシヌクレイン遺伝子新規変異の解析 (2014)
  • Author(s): 吉野浩代、西岡健弥、李元哲、舩山学、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 大脳皮質基底核症候群の髄液マーカーに基づいた臨床解析 (2014)
  • Author(s): 中山茶千子、西岡健弥、原裕子、本井ゆみ子、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] パーキンソン病の家族歴を有する多系統萎縮症患者におけるCOQ2変異解析 (2014)
  • Author(s): 三笠道太、金井数明、李元哲、西岡健弥、舩山学、富山弘幸、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 難治性の慢性疼痛を伴ったパーキンソン病患者へのSCS導入検討 (2014)
  • Author(s): 松島隆史、西岡健弥、藤巻基紀、原毅、中島円、新井一、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Parkinノックアウトマウスにおける細胞骨格蛋白異常による機能障害 (2014)
  • Author(s): 江口博人、今泉美佳、塚口ケネス、舩山学、西岡健弥、波田野琢、斉木臣二、佐藤栄人、久保紳一郎、今井譲、永松信哉、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 日本人パーキンソン病におけるEIF4G1遺伝子変異の頻度 (2014)
  • Author(s): 舩山学、西岡健弥、大垣光太郎、李元哲、佐々木良元、小久保康昌、葛原茂樹、高橋裕秀、富山弘幸、水野美邦、服部信孝
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Genetic Analysis of Parkinson’s Disease in the Japanese population (2013)
  • Author(s): Kenya Nishioka
  • Organizer: GEO-PD Genetic Epidemiology of Parkinson's disease
  • Place of Presentation: ドイツ リューベック
• [Book] 家族性パーキンソン病 update annual review 2016 (2016)
  • Author(s): 松島隆史、西岡健弥、服部信孝
  • Publisher: 中外医学社
• [Book] 第17番染色体に連鎖するパーキソニズムを伴う前側頭葉型認知症（FTDP-17） (2016)
  • Author(s): 西岡健弥，池田彩，服部信孝
  • Publisher: 中外医学社
• [Book] 痛みのScience and Practice (2015)
  • Author(s): 西岡健弥 服部信孝
  • Publisher: 文光堂
• [Book] 神経症候群（第２版）（II）ーその他の神経疾患を含めてー (2014)
  • Author(s): 西岡健弥 服部信孝
  • Publisher: 日本臨床社