Genetic epidemiology of hereditary spastic paraplegia (HSP) in Japan and Identification of novel mutations in HSP genes

• Project/Area Number: 20591009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Jichi Medical University
• Principal Investigator: SHIMAZAKI Haruo Jichi Medical University, 医学部, 講師 (30316517)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝性痙性対麻痺 / 多施設共同研究 / 遺伝子解析 / 連鎖解析 / ARSACS / exome解析

Research Abstract

We have corrected 260 clinical findings and DNAs from Japanese hereditary spastic paraplegia (HSP) families. We could identify several novel mutations of reported HSP genes using our comprehensive genomic analysis systems. Genetic epidemiological finding of HSP in Japan has been becoming clearer. We also revealed new type of HSP with optic atrophy and peripheral neuropathy. Linkage study disclosed that genetic locus of this HSP was assigned to different from other HSP loci. Exome sequencing could identify novel candidate gene mutations for this HSP.

Research Products

• [Journal Article] 常染色体劣性遺伝性痙性対麻痺の臨床-SPG11, ARSACSを中心に (2011)
  • Author(s): 嶋崎晴雄
  • Journal Title: 神経内科 74 Pages: 127-134
• [Journal Article] 遺伝性痙性対麻痺の疫学 (2011)
  • Author(s): 瀧山嘉久, 嶋崎晴雄, 他
  • Journal Title: 神経内科 74 Pages: 141-145
• [Journal Article] 常染色体劣性遺伝性痙性対麻痺の臨床-SPG11,ARSACSを中心に (2011)
  • Author(s): 嶋崎晴雄
  • Journal Title: 神経内科 Volume: 74 Pages: 127-134
• [Journal Article] 遺伝性痙性対麻痺の疫学 (2011)
  • Author(s): 瀧山嘉久, 嶋崎晴雄, ら
  • Journal Title: 神経内科 Volume: 74 Pages: 141-145
• [Journal Article] Adult-onset Alexander disease with typical "tadpole" appearance of the brainstem and unusual involvement of bilateral basal ganglia : a case report and review of the literature. (2010)
  • Author(s): Namekawa M, Shimazaki H, et al.
  • Journal Title: BMC Neurology. 10 Pages: 21-21
  • Peer Reviewed
• [Journal Article] Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo-controlled trial. (2010)
  • Author(s): Katsuno M, Shimazaki H, et al.
  • Journal Title: Lancet Neurology. 9 Pages: 875-884
  • Peer Reviewed
• [Journal Article] 経過中にPosterior reversible encephalopathy syndrome(PRES)と甲状腺癌を合併した視神経脊髄炎の47歳女性例 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Journal Title: 日本内科学会雑誌 99 Pages: 1913-1915
  • NAID: 10026623444
  • Peer Reviewed
• [Journal Article] A型ボツリヌス中毒の82歳男性例 (2010)
  • Author(s): 中村優子, 嶋崎晴雄, 他
  • Journal Title: Neuroin fection 15 Pages: 46-50
• [Journal Article] Adult-onset Alexander disease with typical "tadpole" appearance of the brainstem and unusual involvement of bilateral basal ganglia : a case report and review of the literature. (2010)
  • Author(s): Namekawa M, Shimazaki H, et al.
  • Journal Title: BMC Neurology Volume: 10 Pages: 21-21
  • Peer Reviewed
• [Journal Article] Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study) : a multicentre, randomised, double-blind, placebo-controlled trial. (2010)
  • Author(s): Katsuno M, Shimazaki H, et al
  • Journal Title: Lancet Neurology Volume: 9 Pages: 875-884
  • Peer Reviewed
• [Journal Article] 経過中にPosterior reversible encephalopathy syndrome(PRES)と甲状腺癌を合併した視神経脊髄炎の47歳女性例 (2010)
  • Author(s): 嶋崎晴雄, ら
  • Journal Title: 日本内科学会雑誌 Volume: 99 Pages: 1913-1915
  • NAID: 10026623444
  • Peer Reviewed
• [Journal Article] A型ボツリヌス中毒の82歳男性例 (2010)
  • Author(s): 中村優子, 嶋崎晴雄, ら
  • Journal Title: Neuroinfection Volume: 15 Pages: 46-50
• [Journal Article] Adult-onset Alexander disease with typical "tadpole" appearance of the brainstem and unusual involvement of bilateral basal ganglia : a case report and review of the literature (2010)
  • Author(s): Namekawa M, Shimazaki H, et al.
  • Journal Title: BMC Neurology 10 Pages: 21-21
  • Peer Reviewed
• [Journal Article] 経過中に Posterior reversible encephalopathy syndrome(PRES)と甲状腺癌を合併した視神経脊髄炎の47歳女性例 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Journal Title: 日本内科学会雑誌 99(in press)
  • NAID: 10026623444
  • Peer Reviewed
• [Journal Article] Reversible limbic encephalitis with antibodies against the membranes of neurons of the hippocampus. (2009)
  • Author(s): 嶋崎晴雄, et al.
  • Journal Title: BMJ Case Reports.
  • Peer Reviewed
• [Journal Article] 当科における抗NMDAレセプター抗体関違脳炎3症例の検討 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Journal Title: Neuroinfection 14 Pages: 89-97
• [Journal Article] Reversible limbic encephalitis with antibodies against the membranes of neurons of the hippocampus (2009)
  • Author(s): 嶋崎晴雄, 他
  • Journal Title: BMJ Case Reports doi:10.1136(online)
  • Peer Reviewed
• [Journal Article] 当科における抗NMDAレセプター抗体関連脳炎3症例の検討 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Journal Title: Neuroinfection 14 Pages: 87-89
  • Peer Reviewed
• [Journal Article] Novel SACS mutation in a Belgian family with sacsin-related ataxia. (2008)
  • Author(s): Ouyang Y, Shimazaki H, et al.
  • Journal Title: J Neurol Sci. 264 Pages: 73-76
  • Peer Reviewed
• [Journal Article] A large family with spinocerebellar ataxia type 6 in Iran : clinical and genetic study. (2008)
  • Author(s): 嶋崎晴雄, et al.
  • Journal Title: Arch Iran Med. 11 Pages: 459-462
  • Peer Reviewed
• [Journal Article] Inverse ocular bobbing in a patient with encephalitis associated with antibodies to the N-methyl-D-aspartate receptor. (2008)
  • Author(s): 嶋崎晴雄, et al.
  • Journal Title: Arch Neurol. 65 Pages: 1251-1251
  • Peer Reviewed
• [Journal Article] 大脳にび慢性脳血流低下を認めた孤発性AOA1(ataxia with ocular apraxia type 1)-末梢神経障害を伴う脊髄小脳変陛症の1例 (2008)
  • Author(s): 池田将樹, 嶋崎晴雄, 他
  • Journal Title: 群馬県核医学研究会誌 23 Pages: 17-19
  • Peer Reviewed
• [Journal Article] Novel SACS mutation in a Belgian family with sacsin-related ataxia. (2008)
  • Author(s): Ouyang Y, Shimazaki H, et al.
  • Journal Title: J Neurol Sci 264 Pages: 73-76
  • Peer Reviewed
• [Journal Article] A large family with spinocerebellar ataxia type 6 in Iran : a clinical and genetic study. (2008)
  • Author(s): Shimazaki H, et al.
  • Journal Title: Arch Iran Med 11 Pages: 459-462
  • Peer Reviewed
• [Journal Article] Inverse ocular bobbing in a patient with encephalitis associated with a ntibodies to the N-methyl-D-aspartate receptor. (2008)
  • Author(s): Shimazaki H, et al.
  • Journal Title: Arch Neurol 65 Pages: 1251-1251
  • Peer Reviewed
• [Journal Article] 大脳にび慢性脳血流低下を認めた孤発性AOA1 (ataxia with ocularapraxia type 1)-末梢神経障害を伴う脊髄小脳変性症の1例 (2008)
  • Author(s): 池田将樹, 嶋崎晴雄ら.
  • Journal Title: 群馬県核医学研究会誌 23 Pages: 17-19
  • Peer Reviewed
• [Presentation] 視神経萎縮,末梢神経障害を伴う遺伝性痙性対麻痺症例の臨床像と原因遺伝子検索 (2011)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 平成22年度運動失調に関する調査及び病態機序に関する研究班会議
  • Place of Presentation: 東京
  • Year and Date: 2011-01-14
• [Presentation] spastin蛋白の機能解析 (2011)
  • Author(s): 迫江公己, 嶋崎晴雄, ら
  • Organizer: 平成22年度運動失調に関する調査及び病態機序に関する研究班会議
  • Place of Presentation: 東京
  • Year and Date: 2011-01-14
• [Presentation] 視神経萎縮, 末梢神経障害を伴う遺伝性痙性対麻痺症例の臨床像と原因遺伝子検索 (2011)
  • Author(s): 嶋崎晴雄, ら
  • Organizer: 平成22年度運動失調に関する調査及び病態機序に関する研究班会議
  • Place of Presentation: 東京
  • Year and Date: 2011-01-14
• [Presentation] Impact of Protein Phosphatase PP2A on ATRA-Induced Activation of FoxO3a In Acute Promyelocytic Leukemia Cells. (2010)
  • Author(s): Sakoe Y, Shimazaki H, et al.
  • Organizer: 52nd annual meeting of the American Society of Hematology
  • Place of Presentation: Orlando
  • Year and Date: 2010-12-04
• [Presentation] 視神経萎縮末梢神経障害を伴う遺伝性痙性対麻痺症例の臨床像と,その候補遺伝子解析 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-28
• [Presentation] 視神経萎縮,末梢神経障害を伴う遺伝性痙性対麻痺症例の臨床像と,その候補遺伝子解析 (2010)
  • Author(s): 嶋崎晴雄, ら
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-28
• [Presentation] Charlevoix-Saguenay型劣性遺伝性痙性失調症の1例 (2010)
  • Author(s): 羽賀理恵, 嶋崎晴雄, 他
  • Organizer: 第87回日本神経学会東北地方会
  • Place of Presentation: 山形
  • Year and Date: 2010-09-11
• [Presentation] 当科における常染色体劣性遺伝性脊髄小脳変性症(ARSCD)の遺伝子解析 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS)の頭部MRI所見 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 平成21年度運動失調に関する調査及び病態機序に関する研究班会議
  • Place of Presentation: 東京
  • Year and Date: 2010-01-14
• [Presentation] Autosomal recessive spastic ataxia of Charlevoix-Saguenay(ARSACS)の頭部MRI所見 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 平成21年度運動失調に関する調査及び病態機序に関する研究班会議
  • Place of Presentation: 東京
  • Year and Date: 2010-01-14
• [Presentation] 嶋崎晴雄, 安藤綾子, 中村優子, 神林崇, 田中恵子, 中野今治. Posterior reversible encephalopathy syndrome(PRES)を来たし, 甲状腺癌を合併した視神経脊髄炎の47歳女性例 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第567回日本内科学会関東地方会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-14
• [Presentation] 非ケベックARSACS症例の臨床・分子遺伝学的検討 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第54回日本人類遺伝学会大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] Novel compound heterozygous mutations in a family with Sacsin-related ataxia. (2009)
  • Author(s): Tsugawa J, Shimazaki H, et al.
  • Organizer: 13^<th> International congress of Parkinson's disease and Movement disorders
  • Place of Presentation: Paris
  • Year and Date: 2009-06-11
• [Presentation] SPG17の原因遺伝子seipinのナンセンス変異をヘテロ接合で認めた痙性対麻痺の1家系 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-21
• [Presentation] SPG17の原因遺伝子 seipin のナンセンス変異をヘテロ接合で認めた痙性対麻痺の1家系 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-21
• [Presentation] 遺伝性痙性対麻痺の大規模分子疫学の解明 (2009)
  • Author(s): 石浦浩之, 嶋崎晴雄, 他
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20
• [Presentation] Seipin遺伝子のナンセンス変異をホモ接合で認めた家族性痙性対麻痺の1家系 (2009)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 平成20年度運動失調に関する調査及び病態機序に関する研究班会議
  • Place of Presentation: 東京
  • Year and Date: 2009-01-16
• [Presentation] Seipin遺伝子のナンセンス変異をホモ接合で認めた家族性痙性対麻痺の1家系. (2009)
  • Author(s): 嶋崎晴雄ら.
  • Organizer: 平成20年度運動失調に関する調査及び病態機序に関する研究班会議.
  • Place of Presentation: 東京
  • Year and Date: 2009-01-16
• [Presentation] Novel compound heterozygous mutations in a family with Sacsin-related ataxia (2009)
  • Author(s): Tsugawa J, Shimazaki H, et al.
  • Organizer: 13^<th> International congress of Parkinson's disease and Movement disorders
  • Place of Presentation: Paris
• [Presentation] 当科における抗NMDAレセプター抗体関違脳炎3症例の検討 (2008)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第13回日本神経感染症学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-11
• [Presentation] 当科における抗NMDAレセプター抗体関連脳炎3症例の検討. (2008)
  • Author(s): 嶋崎晴雄ら.
  • Organizer: 第13回日本神経感染症学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-11
• [Presentation] ARSACSのMRI,SPECT所見 (2008)
  • Author(s): 嶋崎晴雄, 他
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15
• [Presentation] ARSACSのMRI, SPECT所見 (2008)
  • Author(s): 嶋崎晴雄ら.
  • Organizer: 第49回日本神経学会総会.
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15
• [Book] 医薬品副作用ハンドブック第2版 (2010)
  • Author(s): 嶋崎晴雄, 他
  • Publisher: 日本臨床社
• [Book] 医薬品副作用ハンドブック 第2版 (2010)
  • Author(s): 嶋崎晴雄, 中野今治
  • Total Pages: 473
  • Publisher: 日本臨床社
• [Book] SCA6, EAOH/AOA1 in Research Advances in Spinocerebellar Ataxia and Spastic Paraplegia. (2008)
  • Author(s): Shimazaki H, Takiyama Y, et al.
  • Publisher: Research Signpost