Search for the causative gene in consanguineous families with Parkinson's disease

• Project/Area Number: 25860725
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• 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), 助教 (40549292)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 家族性パーキンソン病 / オート接合性マッピング / パーキンソン病 / 劣性遺伝性PD / 血族婚

Outline of Final Research Achievements

This study identified 25 candidate variants for Parkinson’s disease by Genome-wide linkage analysis and whole-exome sequencing in four consanguineous families with Parkinson’s disease (FPD). We did not find any of the twenty-five candidate variants in 100 normal Japanese controls. Then, I performed mutation analysis of the 25 candidate variants on 500 patients with FPD. However, we did not detect any mutations. I still cannot conclude whether those 25 variants are the causative mutations for FPD. Therefore, we need further investigations to identify the genes responsible for FPD.

Research Products

• [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] 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] Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort (2016)
  • Author(s): Ryoichi Nakamura, Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe.
  • Journal Title: Neurobiology of Aging Volume: 39 Pages: 219-219
  • DOI: 10.1016/j.neurobiolaging.2015.11.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] 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] 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] P150glued-associated disorders are caused by activation of intrinsic apoptotic pathway. (2014)
  • Author(s): Ishikawa K, Saiki S, Furuya N, Yamada D, Imamichi Y, Li Y, Kawajiri S, Sasaki H, Koike M, Tsuboi Y, Hattori N.
  • Journal Title: PLoS One. Volume: 9 Issue: 4 Pages: e94645-e94645
  • DOI: 10.1371/journal.pone.0094645
  • Peer Reviewed / Open Access
• [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] The evaluation of polyglutamine repeats in autosomal dominant Parkinson's disease. (2014)
  • Author(s): Yamashita C, Tomiyama H, Funayama M, Inamizu S, Ando M, Li Y, Yoshino H, Araki T, Ichikawa T, Ehara Y, Ishikawa K, Mizusawa H, Hattori N.
  • Journal Title: Neurobiol Aging. Volume: 35 Issue: 7 Pages: 1779.e17-1779.e21
  • DOI: 10.1016/j.neurobiolaging.2014.01.022
  • Peer Reviewed / Open Access
• [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] A TREX1 mutation causing cerebral vasculopathy in a patient with familial chilblain lupus. (2013)
  • Author(s): Yamashiro K, Tanaka R, Li Y, Mikasa M, Hattori N.
  • Journal Title: J Neurol Volume: 260 Issue: 10 Pages: 2653-2655
  • DOI: 10.1007/s00415-013-7084-y
  • Peer Reviewed
• [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
  • Organizer: 第55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
• [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
  • Author(s): 李元哲
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡