Functional analysis of a gene possibly responsible for cases with schizophrenia exhibiting unique intermediate phenotypes in a Japanese family

• Project/Area Number: 15K09811
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kagoshima University
• Principal Investigator: NAKAMURA Masayuki 鹿児島大学, 医歯学域医学系, 准教授 (90332832)
• Co-Investigator(Kenkyū-buntansha): 佐野 輝 鹿児島大学, 医歯学域医学系, 教授 (30178800)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 統合失調症 / 中間表現型 / ヒストン修飾 / 統合失調症病因遺伝子

Outline of Final Research Achievements

We performed genetic analysis for a family with both schizophrenic symptoms and unique dysmorphic features. We identified a c.2173C> T (p.Arg725Thr) mutation in the gene X that co-segregates only within patients. The gene X product has a histone modification activity. In the proband derived-lymphoblastoid cells, the gene X expression was significantly decreased when compared to healthy control-derived cells although there was no significant difference in the histone modification activity. These results suggests that histone modification abnormality caused by reduced expression of gene X at a certain stage of development may affect other gene expressions.

Research Products

• [Journal Article] 発熱・白血球増多を伴うカタトニアを呈した急速交代型双極性障害の1例 (2017)
  • Author(s): 石島 洋輔, 新井 薫, 肝付 洋, 中村 雅之, 佐野 輝
  • Journal Title: 精神医学 Volume: 59 Pages: 943-948
  • NAID: 40021339421
  • Peer Reviewed
• [Journal Article] Chorein interacts with alpha-tubulin and HDAC6, and overexpression preserves cell viability during nutrient deprivation in HEK293 cells (2016)
  • Author(s): Sasaki N, Nakamura M, Kodama A, Urata Y, Shiokawa N, Hayashi T, Sano A
  • Journal Title: FASEB J Volume: 30 Issue: 11 Pages: 3726-3732
  • DOI: 10.1096/fj.201500191rr
  • Peer Reviewed
• [Journal Article] The effects of olanzapine treatment on brain regional glucose metabolism in neuroleptic-naive first-episode schizophrenic patients. (2016)
  • Author(s): Yoshimuta H, Nakamura M, Kanda E, Fujita S, Takeuchi K, Fujimoto T, Nakabeppu Y, Akasaki Y, Sano A
  • Journal Title: Hum. Psychopharmacol. Volume: 31 Issue: 6 Pages: 419-416
  • DOI: 10.1002/hup.2558
  • Peer Reviewed
• [Journal Article] Phenotypic abnormalities in a chorea-acanthocytosis mouse model are modulated by strain background. (2016)
  • Author(s): Sakimoto H, Nakamura M, Nagata O, Yokoyama I, Sano A:
  • Journal Title: Biochem Biophys Res Commun Volume: 25 Issue: 1 Pages: 118-124
  • DOI: 10.1016/j.bbrc.2016.02.077
  • Peer Reviewed
• [Journal Article] Seizures as presenting and prominent symptom in Chorea-Acanthocytosis with c.2343del VPS13A gene mutation. (2016)
  • Author(s): Benninger F, Afawi Z, Korczyn AD, Oliver KL, Pendziwiat M, Nakamura M, Sano A, Helbig I, Berkovic SF, Blatt I
  • Journal Title: Eplepsia Volume: 57 Issue: 4 Pages: 549-556
  • DOI: 10.1111/epi.13318
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Case of McLeod syndrome with a novel genetic mutation (2016)
  • Author(s): Narumi S, Natori T, Miyazawa H, Kato T, Yonezawa H, Nishino I, Nakamura M, Sano A, Terayama Y
  • Journal Title: Neurology and Clinical Neuroscience Volume: 印刷中 Issue: 3 Pages: 115-117
  • DOI: 10.1111/ncn3.12042
  • Peer Reviewed
• [Presentation] mtDNA多重欠失を伴うミトコンドリア病の遺伝子解析 (2017)
  • Author(s): 笠毛 渓, 中村 雅之, 大毛 葉子, 梅原 ひろみ, 佐野 輝
  • Organizer: 日本生物学的精神医学会・日本神経精神薬理学会合同年会
• [Presentation] 新規のCSF-1R遺伝子変異が同定された神経軸索スフェロイド形成を伴う遺伝性びまん性白質脳症の一例 (2017)
  • Author(s): 崎元 仁志, 石塚 貴周, 安庭 愛子, 中村 雅之, 佐野 輝
  • Organizer: 日本生物学的精神医学会・日本神経精神薬理学会合同年会
• [Presentation] Effect of genetic background on the phenotype of chorea-acanthocytosis model mouse (2015)
  • Author(s): Sakimoto H, Nagata O, Yokosuka S, Arai K, Nakamura M, Sano A
  • Organizer: 45th annual meeting of the Society for Neuroscience
  • Place of Presentation: Chicago USA
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] Behavioral and sperm motility analyses of male infertility in Chorea-acanthocytosis model mouse (2015)
  • Author(s): Nagata O, Sakimoto H, Yokotsuka S, Arai K, Nakamura M, Sano A
  • Organizer: 45th annual meeting of the Society for Neuroscience
  • Place of Presentation: Chicago USA
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] Chorein /HDAC6 interaction confers resistance to nutrient deprivation in chorein-overexpressing HEK293 cells (2015)
  • Author(s): Nakamura M, Sasaki N, Kodama A, Shiokawa N, Sano A
  • Organizer: 45th annual meeting of the Society for Neuroscience
  • Place of Presentation: Chicago USA
  • Year and Date: 2015-10-18
  • Int'l Joint Research