Searching a causative gene of corticobasal degeneration with next generation sequencing

• Project/Area Number: 15H06601
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: OGAKI Kotaro 順天堂大学, 医学部, 助教 (20459035)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 神経内科 / 大脳皮質基底核変性症 / 遺伝子 / 神経科学 / 次世代シークエンサー / 脳神経疾患

Outline of Final Research Achievements

Corticobasal degeneration (CBD) and conticobasal syndrome (CBS) are rare neurodegenerative disorders. Furthermore, familial CBS is extremely rare. We found familial CBS in which two siblings have CBS and their father had similar symptom. We hypothesized that one causative gene caused this familial disease. In 2015 and 2016, we examined the detailed familial history, neurological examination, neuroimaging and blood sampling for eight members in the family. We extracted DNA from lymphocyte of those eight members. Exome sequencing (high-throughput DNA sequencing for all of the expressed genes in a genome) was done in two siblings with CBS and two healthy family members. In 2016 and 2017, we analyzed genetic data and reduced the number of candidate genes.

Research Products

• [Journal Article] Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism. (2017)
  • Author(s): Puschmann A, Fiesel FC, Caulfield TR, Hudec R, Ando M, Truban D, Hou X, Ogaki K, Heckman MG, James ED, Swanberg M, Jimenez-Ferrer I, Hansson O, Opala G, Siuda J, Boczarska-Jedynak M, Friedman A, Koziorowski D, Aasly JO, Lynch T, Mellick GD, Mohan M, Silburn PA, Sanotsky Y, Vilarino-Guell C, Farrer MJ et al.
  • Journal Title: Brain Volume: 140 Issue: 1 Pages: 98-117
  • DOI: 10.1093/brain/aww261
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reply: Heterozygous PINK1 p.G411S in rapid eye movement sleep behaviour disorder. (2017)
  • Author(s): Puschmann A, Fiesel FC, Caulfield TR, Hudec R, Ando M, Truban D, Hou X, Ogaki K, Heckman MG, James ED, Swanberg M, Jimenez-Ferrer I, Hansson O, Opala G, Siuda J, Boczarska-Jedynak M, Friedman A, Koziorowski D, Aasly JO, Lynch T, Mellick GD, Mohan M, Silburn PA, Sanotsky Y, Vilarino-Guell C, Farrer MJ et al.
  • Journal Title: Brain Volume: in Press Issue: 6 Pages: e33-e33
  • DOI: 10.1093/brain/awx077
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity. (2017)
  • Author(s): Ando M, Fiesel FC, Hudec R, Caulfield TR, Ogaki K, Gorka-Skoczylas P, Koziorowski D, Friedman A, Chen L, Dawson VL, Dawson TM, Bu G, Ross OA, Wszolek ZK, Springer W.
  • Journal Title: Mol Neurodegener. Volume: 12 Issue: 1 Pages: 32-32
  • DOI: 10.1186/s13024-017-0174-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review. (2016)
  • Author(s): Ogaki K, Koga S, Aoki N, Lin W, Suzuki K, Ross OA, Dickson DW.
  • Journal Title: Neuropathology Volume: 36 Issue: 1 Pages: 64-76
  • DOI: 10.1111/neup.12230
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP-C. (2016)
  • Author(s): Koga S, Josephs KA, Ogaki K, Labbe C, Uitti RJ, Graff-Radford N, van Gerpen JA, Cheshire WP, Aoki N, Rademakers R, Wszolek ZK, Ross OA, Dickson DW.
  • Journal Title: Mov Disord. Volume: 31 Issue: 5 Pages: 653-662
  • DOI: 10.1002/mds.26499
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] MAPT haplotype diversity in multiple system atrophy. (2016)
  • Author(s): Labbe C, Heckman MG, Lorenzo-Betancor O, Murray ME, Ogaki K, Soto-Ortolaza AI, Walton RL, Fujioka S, Koga S, Uitti RJ, van Gerpen JA, Petersen RC, Graff-Radford NR, Younkin SG, Boeve BF, Cheshire WP Jr, Low PA, Sandroni P, Coon EA, Singer W, Wszolek ZK, Dickson DW, Ross OA.
  • Journal Title: Parkinsonism Relat Disord. Volume: 30 Pages: 40-45
  • DOI: 10.1016/j.parkreldis.2016.06.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TREM2 p.R47H substitution is not associated with dementia with Lewy bodies. (2016)
  • Author(s): Walton RL, Soto-Ortolaza AI, Murray ME, Lorenzo-Betancor O, Ogaki K, Heckman MG, Rayaprolu S, Rademakers R, Ertekin-Taner N, Uitti RJ, van Gerpen JA, Wszolek ZK, Smith GE, Kantarci K, Lowe VJ, Parisi JE, Jones DT, Savica R, Graff-Radford J, Knopman DS, Petersen RC, Graff-Radford NR, Ferman TJ, Dickson DW et al.
  • Journal Title: Neurol Genet. Volume: 2 Issue: 4
  • DOI: 10.1212/nxg.0000000000000085
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Parkinson’s disease (2016)
  • Author(s): 大垣 光太郎, 古賀 俊輔, Michael G Heckman, Fabienne C Fiesel, 安藤 真矢, 西岡 健弥, 舩山 学, Bradley Boeve, Wolfdieter Springer, Zbigniew K Wszolek, Dennis W. Dickson, 服部 信孝, Owen A Ross.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2016-05-18
• [Book] 遺伝子医学MOOK別冊 シリーズ：最新遺伝医学研究と遺伝カウンセリング シリーズ2 「最新精神・神経遺伝医学研究と遺伝カウンセリング」パーキンソン病の遺伝子研究 (2017)
  • Author(s): 大垣光太郎 西岡健弥 服部信孝
  • Total Pages: 308
  • Publisher: 株式会社メディカル ドゥ