Analysis of genetic back ground and pathomechanism of spinocerebellar degeneration

• Project/Area Number: 15K09344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: DOI Hiroshi 横浜市立大学, 医学部, 准教授 (10326035)
• Co-Investigator(Kenkyū-buntansha): 田中 章景 横浜市立大学, 医学研究科, 教授 (30378012) ; 田中 健一 横浜市立大学, 医学部, 助教 (50722881) ; 國井 美紗子 横浜市立大学, 附属病院, 助教 (80725200)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Naomichi 横浜市立大学, 医学研究科, 教授 (80325638) ; ISHIKAWA Kinya 東京医科歯科大学, 医学部附属病院, 教授 (30313240)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 脊髄小脳変性症 / exome / エクソーム

Outline of Final Research Achievements

In this study, we aimed to identify novel genes responsible for spinocerebellar degeneration (SCD), through the exome analysis of familial or sporadic cases with SCD, who did not have known SCD-related mutations,
As results of exome analysis for an autosomal dominant SCD family, we identified a missense mutation of CACNA1G, encoding voltage gated calcium channel. However, during our study, the mutation was reported as the novel cause of SCD by other groups. We are preparing a paper focused on the pathology of the patients.
As the results of exome analysis for recessive or sporadic SCD cases, we identified four patients from three families of SCD with ERCC4 mutation. We reported ERCC4 mutations as the rare cause of SCD.

Research Products

• [Journal Article] Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations (2018)
  • Author(s): Doi H、Koyano S、Miyatake S、Nakajima S、Nakazawa Y、Kunii M、Tomita-Katsumoto A、Oda K、Yamaguchi Y、Fukai R、Ikeda S、Kato R、Ogata K、Kubota S、Hayashi N、Takahashi K、Tada M、Tanaka K、Nakashima M、Tsurusaki Y et al.
  • Journal Title: Journal of Human Genetics Volume: 63 Issue: 4 Pages: 417-423
  • DOI: 10.1038/s10038-017-0408-5
  • Peer Reviewed / Open Access
• [Journal Article] Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel (2018)
  • Author(s): Kunii M.、Doi H.、Ishii Y.、Ohba C.、Tanaka K.、Tada M.、Fukai R.、Hashiguchi S.、Kishida H.、Ueda N.、Kudo Y.、Kugimoto C.、Nakano T.、Udaka N.、Miyatake S.、Miyake N.、Saitsu H.、Ito Y.、Takahashi K.、Nakamura H.、Tomita-Katsumoto A.、Takeuchi H.、Koyano S.、Matsumoto N.、Tanaka F.
  • Journal Title: Clinical Genetics Volume: - Issue: 2 Pages: 232-238
  • DOI: 10.1111/cge.13371
  • Peer Reviewed
• [Journal Article] A Japanese Family of Spinocerebellar Ataxia Type 21: Clinical and Neuropathological Studies (2018)
  • Author(s): Yahikozawa Hiroyuki、Miyatake Satoko、Sakai Toshiaki、Uehara Takeshi、Yamada Mitsunori、Hanyu Norinao、Futatsugi Yasuhiro、Doi Hiroshi、Koyano Shigeru、Tanaka Fumiaki、Suzuki Atsushi、Matsumoto Naomichi、Yoshida Kunihiro
  • Journal Title: The Cerebellum Volume: 印刷中 Issue: 5 Pages: 525-530
  • DOI: 10.1007/s12311-018-0941-6
  • Peer Reviewed
• [Journal Article] Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis (2018)
  • Author(s): Tada Mikiko、Doi Hiroshi、Koyano Shigeru、Kubota Shun、Fukai Ryoko、Hashiguchi Shunta、Hayashi Noriko、Kawamoto Yuko、Kunii Misako、Tanaka Kenichi、Takahashi Keita、Ogawa Yuki、Iwata Ryo、Yamanaka Shoji、Takeuchi Hideyuki、Tanaka Fumiaki
  • Journal Title: The American Journal of Pathology Volume: 188 Issue: 2 Pages: 507-514
  • DOI: 10.1016/j.ajpath.2017.10.007
  • Peer Reviewed
• [Journal Article] MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment. (2017)
  • Author(s): Satake T, Yamashita K, Hayashi K, Miyatake S, Tamura-Nakano M, Doi H, Furuta Y, Shioi G, Miura E, Takeo YH, Yoshida K, Yahikozawa H, Matsumoto N, Yuzaki M, Suzuki A.
  • Journal Title: EMBOJ Volume: 36 Issue: 9 Pages: 1227-1242
  • DOI: 10.15252/embj.201695630
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 孤発性ALSの早期診断 (2017)
  • Author(s): 土井 宏、田中章景
  • Journal Title: 神経内科 Volume: 86 Pages: 9-16
• [Journal Article] Relationship between cortex and pulvinar abnormalities on diffusion-weighted imaging in status epilepticus. (2016)
  • Author(s): Nakae Y, Kudo Y, Yamamoto R, Dobashi Y, Kawabata Y, Ikeda S, Yokoyama M, Higashiyama Y, Doi H, Johkura K, Tanaka F.
  • Journal Title: J Neurol. Volume: 263 Issue: 1 Pages: 127-132
  • DOI: 10.1007/s00415-015-7948-4
  • Peer Reviewed
• [Journal Article] Autosomal recessive spinocerebellar ataxias in Japan (2016)
  • Author(s): 田中章景、土井 宏、國井美紗子
  • Journal Title: Rinsho Shinkeigaku Volume: 56 Issue: 6 Pages: 395-399
  • DOI: 10.5692/clinicalneurol.cn-000879
  • NAID: 130005158857
  • ISSN: 0009-918X, 1882-0654
• [Journal Article] Clinicopathologic features of folate-deficiency neuropathy. (2015)
  • Author(s): Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, Katsuno M, Doi H, Tanaka F, Sobue G.
  • Journal Title: Neurology Volume: 84 Issue: 10 Pages: 1026-1033
  • DOI: 10.1212/wnl.0000000000001343
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis. (2015)
  • Author(s): Kino Y, Washizu C, Kurosawa M, Yamada M, Miyazaki H, Akagi T, Hashikawa T, Doi H, Takumi T, Hicks GG, Hattori N, Shimogori T, Nukina N.
  • Journal Title: Acta Neuropathol Commun Volume: 3 Issue: 1 Pages: 24-24
  • DOI: 10.1186/s40478-015-0202-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel mutation in ELOVL4 leading to spinocerebellar ataxia (SCA) with the hot cross bun sign but lacking erythrokeratodermia: a broadened spectrum of SCA34. (2015)
  • Author(s): Ozaki K, Doi H, Mitsui J, Sato N, Iikuni Y, Majima T, Yamane K, Irioka T, Ishiura H, Doi K, Morishita S, Higashi M, Sekiguchi T, Koyama K, Ueda N, Miura Y, Miyatake S, Matsumoto N, Yokota T, Tanaka F, Tsuji S, Mizusawa H, Ishikawa K.
  • Journal Title: JAMA Neurology Volume: 72 Issue: 7 Pages: 797-805
  • DOI: 10.1001/jamaneurol.2015.0610
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Exome analysis of autosomal recessive or sporadic cases of cerebellar ataxia and spastic paraplegia. (2017)
  • Author(s): Doi H., Koyano S., Kunii M., Miyatake S., Nakajima S., Hashiguchi S., Ikeda S., Kubota S., Hirama N., Ogawa Y., Takahashi K., Tada M., Tanaka K., Takeuchi H., Matsumoto N., Tanaka F.
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] The clinical and pathological features of autosomal-dominant SCA with CACNA1G mutation. (2016)
  • Author(s): Doi H, Koyano S, Shiina M, Ogata K, Hirashima F, Inoue Y, Hashiguchi S, Kunii M, Kishida H, Yokota T, Mizusawa H, Mitsui J, Tsuji S, Matsumoto N, Ishikawa K and Tanaka F.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際会議場（兵庫）
• [Presentation] Late-onset spastic ataxia phenotype related to a novel homozygous DDHD2 mutation. (2015)
  • Author(s): 土井宏，吉田邦広，牛山雅夫，谷佳津子，松本直通，田中章景
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟）
  • Year and Date: 2015-05-23
• [Book] 前頭側頭葉変性症療養の手引き 「前頭側頭葉変性症の経過」 (2017)
  • Author(s): 土井 宏、田中章景
  • Total Pages: 70
  • Publisher: 平成28年度厚生労働科学研究費補助金 難治性疾患等政策研究事業（難治性疾患政策研究事業）「神経変性疾患領域における基盤的調査研究」班