The detection of modifier gens in alpha-synuclein multiplications

2016 Fiscal Year Annual Research Report

• Project/Area Number: 25860726
• Research Institution: Juntendo University
• Principal Investigator: 西岡 健弥 順天堂大学, 医学部, 准教授 (40348933)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 遺伝子 / DNA / パーキンソン病 / 二倍体 / SNCA

Outline of Annual Research Achievements

SNCA遺伝子に2倍体変異を有した患者合計20名(6家系、男性：女性=8：12、パーキンソン病発症11名、パーキンソン病非発症キャリア9名)を収集した。同時に詳細な臨床情報も集めた．臨床経過の詳細な聴取，Unified Parkinson’s Disease Rating Scale , revised-Hasegawa Dementing Scale, Mini-Mnetal state examination, 薬剤反応性，精神疾患の有無，またパーキンソン病の診断に関連する頭部MRI，MIBG myocardial scintigraphy, brain SPECT, DAT scanといった画像検査を施行した．次に遺伝子発現量の算出を行った．具体的にはAffymetrixのGeneChip（Genome-Wide Human SNP array 6.0）を用いて、各サンプルにおける一塩基多型(Single Nucleotide Polymorphism: SNP)を調べた。各家系の家系図を用いPedin.preファイル、CHP Mapping filesを作成し、SNP HiTLink　v1.5.1を使用し、lkin fileを作成した。この作成したlkin fileを基に、連鎖解析ソフトであるMERLIN（University of Michigan）を用いてLOD scoreを算出し、このデータを用いて散布図を作成し、ゲノムワイド関連解析プロット：Manhattan plotの図を作成した．これらの解析からLOD score3以上で算出される領域として全染色体の中から18領域同定を行った．現在これらの遺伝子に対してscreeningを施行し，発症者，非発症者の相違がないかどうか，確認を行っている．

Research Products

• [Journal Article] A novel mutation of CHCHD2 p.R8H in a sporadic case of Parkinson's disease. (2017)
  • Author(s): Ikeda A, Matsushima T, Daida K, Nakajima S, Conedera S, Li Y, Yoshino H, Oyama G, Funayama M, Nishioka K, Hattori N.
  • Journal Title: Parkinsonism and related disorders Volume: 34 Pages: 66-68
  • DOI: 10.1016/j.parkreldis.2016.10.018.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Genotype-phenotype correlations of cysteine replacement in CADASIL. (2017)
  • Author(s): Matsushima T, Conedera S, Tanaka R, Li Y, Yoshino H, Funayama M, Ikeda A, Hosaka Y, Okuzumi A, Shimada Y, Yamashiro K, Motoi Y, Nishioka K, Hattori N.
  • Journal Title: Neurobiology of Aging Volume: 50 Pages: XX-XX
  • DOI: 10.1016/j.neurobiolaging.2016.10.026.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] FBXO7 Mutations in Parkinson's Disease and Multiple System Atrophy. (2016)
  • Author(s): Conedera S, Apaydin H, Li Y, Yoshino H, Ikeda A, Matsushima T, Funayama M, Nishioka K, Hattori N.
  • Journal Title: Neurobiology of Aging Volume: 40 Pages: e1-5
  • 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, Nagata T, Shinagawa S, Kobayashi N, Ohnuma T, Takeshita Y, Kawai E, Takayama T, Nishioka K, Motoi Y, Hattori N, Nakayama K, Yamada H, Arai H.
  • Journal Title: Dementia and Geriatric Cognitive Disorders Extra Volume: 16 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 and related disorders Volume: 25 Pages: 108-109
  • DOI: 10.1016/j.parkreldis.2016.01.028.
  • Peer Reviewed / Acknowledgement Compliant
• [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 Pages: XX-XX
  • DOI: 10.1002/gps.4600.
  • 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 – 2016-10-08
  • 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 – 2016-05-21
• [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 – 2016-05-21
• [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 – 2016-05-21
• [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
  • Total Pages: XX-XX
  • 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
  • Total Pages: XX-XX
  • Publisher: 中外医学社