Mutational analysis of the CHCHD2 gene in neurodegenerative diseases

• Project/Area Number: 16K09700
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Li Yuanzhe 順天堂大学, 医学(系)研究科(研究院), 特任助教 (40549292)
• Research Collaborator: IKEDA aya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: CHCHD2 / 家族性パーキンソン病

Outline of Final Research Achievements

We recently identified mutations in the coiled-coil-helix coiled-coil-helix domain containing 2 (CHCHD2) gene in Japanese families with autosomal dominant Parkinson’s disease. We obtained 944 amyotrophic lateral sclerosis (ALS) patients from Japanese Consortium for Amyotrophic Lateral Sclerosis Research. The CHCHD2 gene was assessed in these patients by Sanger sequence. And we screened for variants and evaluated allele frequency. We referred allele frequency of control subjects in Human Genetic Variation Database to compare with that of ALS.　We found four variants on the CHCHD2 region in ALS patients. We identified one novel variant in untranslated region and three variants that had been previously reported. Allele frequencies of three variants did not differ between ALS patients and control subjects.

Academic Significance and Societal Importance of the Research Achievements

CHCHD2はさまざまな疾患の関連が示唆されているものの、ゲノム解析からアプローチした報告は不十分である。本研究ではこれまで全く研究報告のないミトコンドリア機能低下が病態に重要であると指摘されているALSについて大規模のゲノム解析を行った。
カスタムパネルの作成より構築されたパーキンソン病関連遺伝子を網羅的に解析できるシステムはパーキンソン病の臨床-ゲノムデータベースの基盤となるゲノム情報蓄積に非常に有用である。

Research Products

• [Journal Article] Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features (2019)
  • Author(s): Ikeda Aya、Shimada Hitoshi、Nishioka Kenya、Takanashi Masashi、Hayashida Arisa、Li Yuanzhe、Yoshino Hiroyo、Funayama Manabu、Ueno Yuji、Hatano Taku、Sahara Naruhiko、Suhara Tetsuya、Higuchi Makoto、Hattori Nobutaka
  • Journal Title: Movement Disorders Volume: 34 Issue: 4 Pages: 568-574
  • DOI: 10.1002/mds.27623
  • Peer Reviewed / Open Access
• [Journal Article] Isolated nigral degeneration without pathological protein aggregation in autopsied brains with LRRK2 p.R1441H homozygous and heterozygous mutations (2018)
  • Author(s): Takanashi M, Funayama M (Contributed equally), Matsuura E, Yoshino H, Li Y, Tsuyama S, Takashima H, Nishioka K, Hattori N
  • Journal Title: Acta Neuropathologica Communications Volume: 6 Issue: 1 Pages: 105-105
  • DOI: 10.1186/s40478-018-0617-y
  • Peer Reviewed / Open Access
• [Journal Article] GCH1 mutations in dopa-responsive dystonia and Parkinson's disease. (2018)
  • Author(s): Yoshino H, Nishioka K, Li Y, Oji Y, Oyama G, Hatano T, Machida Y, Shimo Y, Hayashida A, Ikeda A, Mogushi K, Shibagaki Y, Hosaka A, Iwanaga H, Fujitake J, Ohi T, Miyazaki D, Sekijima Y, Oki M, Kusaka H, Fujimoto KI Ugawa Y, Funayama M, Hattori N.
  • Journal Title: Journal of Neurology Volume: 265(8) Issue: 8 Pages: 1860-1870
  • DOI: 10.1007/s00415-018-8930-8
  • Peer Reviewed / Open Access
• [Journal Article] Genetic analysis of TMEM230 in Japanese patients with familial Parkinson’s disease. (2018)
  • Author(s): Conedera SA, Li Y, Funayama M, Yoshino H, Nishioka K, Hattori N.
  • Journal Title: Parkinsonism Relat Disord Volume: 48 Pages: 107-108
  • DOI: 10.1016/j.parkreldis.2017.12.020
  • Peer Reviewed
• [Journal Article] Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. (2018)
  • Author(s): Fujimaki M, Saiki S, Li Y, Kaga N, Taka H, Hatano T, Ishikawa KI, Oji Y, Mori A, Okuzumi A, Koinuma T, Ueno SI, Imamichi Y, Ueno T, Miura Y, Funayama M, Hattori N.
  • Journal Title: Neurology. Volume: 90 Issue: 5 Pages: 1-8
  • DOI: 10.1212/wnl.0000000000004888
  • Peer Reviewed / Open Access
• [Journal Article] COQ2 variants in Parkinson's disease and multiple system atrophy. (2018)
  • Author(s): Mikasa M, Kanai K, Li Y, Yoshino H, Mogushi K, Hayashida A, Ikeda A, Kawajiri S, Okuma Y, Kashihara K, Sato T, Kondo H, Funayama M, Nishioka K, Hattori N.
  • Journal Title: J Neural Transm (Vienna) Volume: - Issue: 6 Pages: 938-944
  • DOI: 10.1007/s00702-018-1885-1
  • Peer Reviewed / Open Access
• [Journal Article] Lysosomal defects in ATP13A2 and GBA associated familial Parkinson's disease. (2017)
  • Author(s): Sato S, Li Y, Hattori N.
  • Journal Title: J Neural Transm Volume: 124 Issue: 11 Pages: 1395-1400
  • DOI: 10.1007/s00702-017-1779-7
  • Peer Reviewed / Open Access
• [Journal Article] <i>CSF1R</i> Mutation p.G589R and the Distribution Pattern of Brain Calcification (2017)
  • Author(s): Daida K, Nishioka K, Li Y, Nakajima S, Tanaka R, Hattori N.
  • Journal Title: Internal Medicine Volume: 56 Issue: 18 Pages: 2507-2512
  • DOI: 10.2169/internalmedicine.8462-16
  • NAID: 130006078597
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Homozygous alpha-synuclein p.A53V in familial Parkinson's disease. (2017)
  • Author(s): Yoshino H, Hirano M, Stoessl AJ, Imamichi Y, Ikeda A, Li Y, Funayama M, Yamada I, Nakamura Y, Sossi V, Farrer MJ, Nishioka K, Hattori N.
  • Journal Title: Neurobiology of Aging Volume: 57 Pages: 248.e7-248.e12
  • DOI: 10.1016/j.neurobiolaging.2017.05.022
  • Peer Reviewed / Open Access
• [Journal Article] Dystonia due to bilateral caudate hemorrhage associated with a COL4A1 mutation. (2017)
  • Author(s): Hatano T, Daida K, Hoshino Y, Li Y, Saitsu H, Matsumoto N, Hattori N.
  • Journal Title: Parkinsonism and Related Disorders Volume: 40 Pages: 80-82
  • DOI: 10.1016/j.parkreldis.2017.04.009
  • Peer Reviewed
• [Journal Article] Parkinsonism in a patient with valosin-containing protein gene mutation showing: a case report. (2017)
  • Author(s): Fujimaki M, Kanai K, Funabe S, Takanashi M, Yokoyama K, Li Y, Hattori N.
  • Journal Title: J Neurol Volume: 264 Issue: 6 Pages: 1284-1286
  • DOI: 10.1007/s00415-017-8467-2
  • Peer Reviewed / Open Access
• [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] Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism. (2017)
  • Author(s): Yamashita C, Funayama M, Li Y, Yoshino H, Yamada H, Seino Y, Tomiyama H, Hattori N.
  • Journal Title: J Neural Transm Volume: 4 Issue: 4 Pages: 431-435
  • DOI: 10.1007/s00702-016-1658-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of the caudate nucleus head and its networks in sporadic amyotrophic lateral sclerosis-frontotemporal dementia continuum. (2016)
  • Author(s): Masuda, M., Senda, J., Watanabe, H., Epifanio, B., Tanaka, Y., Imai, K., Riku, Y., Li, Y., Nakamura, R., Ito, M., Ishigaki, S., Atsuta, N., Koike, H., Katsuno, M., Hattori, N., Naganawa, S., and Sobue, G.
  • Journal Title: Amyotroph Lateral Scler Frontotemporal Degener Volume: 17 Issue: 7-8 Pages: 571-579
  • DOI: 10.1080/21678421.2016.1211151
  • Peer Reviewed / Open Access
• [Journal Article] A family with hereditary diffuse leukoencephalopathy with spheroids caused by a novel c.2442+2T>C mutation in the CSF1R gene. (2016)
  • Author(s): Kawakami I, Iseki E, Kasanuki K, Minegishi M, Sato K, Hino H, Shibuya K, Fujisawa K, Higashi S, Akiyama H, Furuta A, Takanashi M, Li Y, Hattori N, Mitsuyama Y, Arai H.
  • Journal Title: Journal of Neuroogicall Science Volume: 15;367 Pages: 349-55
  • DOI: 10.1016/j.jns.2016.06.013
  • Peer Reviewed / Open Access
• [Journal Article] Absence of Lewy pathology associated with PINK1 homozygous mutation. (2016)
  • Author(s): Takanashi M, Li Y, Hattori N.
  • Journal Title: Neurology. Volume: 86 Issue: 23 Pages: 2212-2213
  • DOI: 10.1212/wnl.0000000000002744
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] パーキンソン病における次世代シークエンサによる遺伝子解析 (2017)
  • Author(s): 李元哲 、吉野浩代 、Silvio Conedera、舩山学、西岡健弥、服部信孝.
  • Organizer: 日本人類遺伝学会第62回大会