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Exome analysis of spinocerebellar ataxias

Research Project

Project/Area Number 24790893
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionYokohama City University

Principal Investigator

DOI Hiroshi  横浜市立大学, 医学部, 講師 (10326035)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsエクソーム / 脊髄小脳変性症
Research Abstract

We aimed to identify the novel causative genes of spinocerebellar ataxia (SCA) by analyzing the exomes of two autosomal recessive SCA (ARSCA), and two autosomal dominant SCA families. As the results, we identified a homozygous mutation of GeneX as the causative agent in one of the ARSCA families. Because GeneX was reported as causative gene for ARSCA-related disease during our study, we added the experiments and revealed that loss of enzymatic activity of GeneX product is the cause of the disease. In relation to this study, we corrected DNAs of 8 ARSCA-suspected families, and conducted exome sequencing for the index cases. We identified and reported the first Japanese case of SPG7 and myoclonus epilepsy with SCARB2 mutation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (36 results)

All 2013 2012 Other

All Journal Article (30 results) (of which Peer Reviewed: 26 results) Presentation (4 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Identification of a novel homozygous SPG7 mutation in a Japanese patient with spastic ataxia : efficient diagnosis by exome sequencing for autosomal recessive cerebellar ataxia and spastic paraplegia2013

    • Author(s)
      Doi H, Ohba C, Tsurusaki Y, Miyatake S, Miyake N, Saitsu H, Kawamoto Y, Yoshida T, Koyano S, Suzuki Y, Kuroiwa Y, Tanaka F and Matsumoto N
    • Journal Title

      Intern Med

      Volume: 52(14) Pages: 1629-1633

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy2013

    • Author(s)
      Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Vaz R, Ceyhan O, Brownstein CA, Swanson LC, Monnot S, Romero NB, Amthor H, Kresoje N, Sivadorai P, Kiraly-Borri C, Haliloglu G, Talim B, Orhan D, Kale G, Charles AK, Fabian VA, Davis MR, Lammens M, Sewry CA, Manzur A, Muntoni F, Clarke NF, North KN, Bertini E, Nevo Y, Willichowski E, Silberg IE, Topaloglu H, Beggs AH, Allcock RJ, Nishino I, Wallgren-Pettersson C, Matsumoto N, Laing NG
    • Journal Title

      Am J Hum Genet

      Volume: 93(1) Pages: 6-18

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Olfactory impairment and pathology in neurodegenerative disorders with brain iron accumulation2013

    • Author(s)
      Dziewulska D, Doi H, Fasano A, Erro R, Fatehi F, Fekete R, Gatto EM, Pablos EG, Lehn A, Miyajima H, Piperno A, Pellechia MT, Wu YR, Yoshida K, Zarruk JG, Jingli S, Schrag A, McNeill A
    • Journal Title

      Acta Neuropathol

      Volume: 126(1) Pages: 151-3

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel SCARB2 mutation causing late-onset progressive myoclonus epilepsy2013

    • Author(s)
      Higashiyama Y, Doi H, Wakabayashi M, Tsurusaki Y, Miyake N, Saitsu H, Ohba C, Fukai R, Miyatake S, Joki H, Koyano S, Suzuki Y, Tanaka F, Kuroiwa Y, Matsumoto N
    • Journal Title

      Mov Disord

      Volume: 28(4) Pages: 552-553

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation2013

    • Author(s)
      Miyake N, Yano S, Sakai C, Hatakeyama H, Matsushima Y, Shiina M, Watanabe Y, Bartley J, Abdenur JE, Wang RY, Chang R, Tsurusaki Y, Doi H, Nakashima M, Saitsu H, Ogata K, Goto Y, Matsumoto N
    • Journal Title

      Hum Mutat

      Volume: 34(3) Pages: 446-452

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phenotypic spectrum of COL4A1 mutations : porencephaly to schizencephaly2013

    • Author(s)
      Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, Kakita A, Yamamoto T, Otsuki Y, Shimizu S, Wada T, Koyama N, Mino Y, Kondo N, Takahashi S, Hirabayashi S, Takanashi J, Okumura A, Kumagai T, Hirai S, Nabetani M, Saitoh S, Hattori A, Yamasaki M, Kumakura A, Sugo Y, Nishiyama K, Miyatake S, Tsurusaki Y, Doi H, Miyake N, Matsumoto N, Saitsu H
    • Journal Title

      Ann Neurol

      Volume: 73(1) Pages: 48-57

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The diagnostic utility of exome sequencing in Joubert syndrome and related disorders2013

    • Author(s)
      Tsurusaki Y, Kobayashi Y, Hisano M, Ito S, Doi H, Nakashima M, Saitsu H, Matsumoto N, Miyake N
    • Journal Title

      J Hum Genet

      Volume: 58(2) Pages: 113-115

    • NAID

      10031156434

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel homozygous SPG7 mutation in a Japanese patient with spastic ataxia: making an efficient diagnosis using exome sequencing for autosomal recessive cerebellar ataxia and spastic paraplegia.2013

    • Author(s)
      Doi H, Ohba C, Tsurusaki Y, Miyatake S, Miyake N, Saitsu H, Kawamoto Y, Yoshida T, Koyano S, Suzuki Y, Kuroiwa Y, Tanaka F and Matsumoto N.
    • Journal Title

      Intern Med

      Volume: 52 Pages: 1629-1633

    • NAID

      130003365707

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy2013

    • Author(s)
      Ravenscroft G, Ogata K, Shiina M, Matsumoto N, Laing NG et al.
    • Journal Title

      Am J Hum Genet

      Volume: 93 Issue: 1 Pages: 6-18

    • DOI

      10.1016/j.ajhg.2013.05.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic utility of whole exome sequencing in cerebellar atrophy in childhood.2013

    • Author(s)
      Ohba C, Osaka H, Iai M, Yamashita S, Suzuki S, Aida N, Doi H, Tomita-Katsumoto A, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Tanaka F, *Matsumoto N, *Saitsu H (*: co-correspondence).
    • Journal Title

      Neurogenet

      Volume: 14 Issue: 3-4 Pages: 225-232

    • DOI

      10.1007/s10048-013-0375-8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Olfactory impairment and pathology in neurodegenerative disorders with brain iron accumulation.2013

    • Author(s)
      Dziewulska D, Doi H, Fasano A, Erro R, Fatehi F, Fekete R, Gatto EM, Pablos EG, Lehn A, Miyajima H, Piperno A, Pellechia MT, Wu YR, Yoshida K, Zarruk JG, Jingli S, Schrag A, McNeill A.
    • Journal Title

      Acta Neuropathol

      Volume: 126 Issue: 1 Pages: 151-153

    • DOI

      10.1007/s00401-013-1136-3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenic mutations in two families with congenital cataract identified with whole-exome sequencing.2013

    • Author(s)
      Kondo Y, Saitsu H, Miyamoto T, Lee BJ, Nishiyama K, Nakashima M, Tsurusaki Y, Doi H, Miyake N, Kim JH, Yu YS, Matsumoto N.
    • Journal Title

      Mol Vis

      Volume: 19 Pages: 384-389

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition Microphthalmia with Limb Anomalies-like.2013

    • Author(s)
      Kondo Y, Koshimizu E, Megarbane A, Hamanoue H, Okada I, Nishiyama K, Kodera H, Miyatake S, Tsurusaki Y, Nakashima M, Doi H, Miyake N, Saitsu H, *Matsumoto N.
    • Journal Title

      Am J Med Genet Part A

      Volume: 161A Issue: 7 Pages: 1543-1546

    • DOI

      10.1002/ajmg.a.35983

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CBSと関連する遺伝子変異2013

    • Author(s)
      土井 宏、田中 章景
    • Journal Title

      臨床神経

      Volume: 53 Pages: 1026-1028

    • NAID

      130004505325

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Identification of a novel homozygous SPG7 mutation in a Japanese patient with spastic ataxia2013

    • Author(s)
      Doi H, Ohba C, Tsurusaki Y, Miyatake S, Miyake N, Saitsu H, Kawamoto Y, Yoshida T, Koyano S, Suzuki Y, Kuroiwa Y, Tanaka F and Matsumoto N
    • Journal Title

      Intern Med

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel SCARB2 mutation causing late-onset progressive myoclonus epilepsy2013

    • Author(s)
      Higashiyama Y, Doi H, Wakabayashi M, Tsurusaki Y, Miyake N, Saitsu H, Ohba C, Fukai R, Miyatake S, Joki H, Koyano S, Suzuki Y, Tanaka F, Kuroiwa Y, Matsumoto N
    • Journal Title

      Mov Disord

      Volume: 28 Issue: 4 Pages: 552-553

    • DOI

      10.1002/mds.25296

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly2013

    • Author(s)
      Yoneda Y, Haginoya K,…..*Saitsu H
    • Journal Title

      Ann Neurol

      Volume: 73(1):48-57 Issue: 1 Pages: 48-57

    • DOI

      10.1002/ana.23736

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation2013

    • Author(s)
      Miyake N^<#>, Yano S^<#> (# denotes equal contribution), Sakai C, Hatakeyama H, Shiina M, Watanabe Y, Bartley J, Abdenur JE, Wang RY, Chang R, Tsurusaki Y, Doi H, Saitsu H, Ogata K, Goto Y, *Matsumoto N
    • Journal Title

      Hum Mut

      Volume: 34(3):446-452 Issue: 3 Pages: 446-452

    • DOI

      10.1002/humu.22257

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The diagnostic utility of exome sequencing in Joubert syndrome related disorders2013

    • Author(s)
      Tsurusaki Y, Kobayashi Y, Hisano M, Ito S, Doi H, Nakashima M, Saitsu H, Matsumoto N, Miyake N
    • Journal Title

      J Hum Genet

      Volume: 58(2):113-115 Issue: 2 Pages: 113-115

    • DOI

      10.1038/jhg.2012.117

    • NAID

      10031156434

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CBSと関連する遺伝子変異2013

    • Author(s)
      土井宏、田中章景
    • Journal Title

      Brain Nerve

      Volume: 65 Pages: 19-30

    • NAID

      130004505325

    • Related Report
      2012 Research-status Report
  • [Journal Article] ALSのパーソナルゲノム解析2013

    • Author(s)
      田中章景、曽根淳、熱田直樹、中村亮一、土井宏、児矢野繁、祖父江元
    • Journal Title

      Brain Nerve

      Volume: 65 Pages: 257-265

    • Related Report
      2012 Research-status Report
  • [Journal Article] Sibling cases of moyamoya disease having homozygous and heterozygous c.14576G>A variant in RNF213 showed varying clinical course and severity2012

    • Author(s)
      Miyatake S, Touho H, Miyake N, Ohba C, Doi H, Saitsu H, Taguri M, Morita S, Matsumoto N
    • Journal Title

      J Hum Genet

      Volume: 57(12) Pages: 804-806

    • NAID

      10031145889

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome2012

    • Author(s)
      Saitsu H, Kato M, Koide A, Goto T, Fujita T, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Hayasaka K, Matsumoto N
    • Journal Title

      Ann Neurol

      Volume: 72(2) Pages: 298-300

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel SACS mutation in an atypical case with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS)2012

    • Author(s)
      Miyatake S, Miyake N, Doi H, Saitsu H, Ogata K, Kawai M, Matsumoto N
    • Journal Title

      Intern Med

      Volume: 51(16) Pages: 2221-2226

    • NAID

      130002062292

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sibling cases of moyamoya disease having homozygous and heterozygous c.14576G>A variant in RNF213 showed varying clinical course and severity.2012

    • Author(s)
      Miyatake S
    • Journal Title

      J Hum Genet.

      Volume: 57 Issue: 12 Pages: 804-806

    • DOI

      10.1038/jhg.2012.105

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome2012

    • Author(s)
      *Saitsu H et al.
    • Journal Title

      Ann Neurol

      Volume: 72(2):298-300 Issue: 2 Pages: 298-300

    • DOI

      10.1002/ana.23620

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel SACS mutation in an atypical case with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).2012

    • Author(s)
      Miyatake S, Miyake N, Doi H, Saitsu H, Ogata K, Kawai M, Matsumoto N.
    • Journal Title

      Intern Med

      Volume: 51 Pages: 2221-2226

    • NAID

      130002062292

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity.2012

    • Author(s)
      Tsurusaki Y, Saitoh S, Tomizawa K, Sudo A, Asahina N, Shiraishi H, Ito J, Tanaka H, Doi H, Saitsu H, Miyake N, Matsumoto N.
    • Journal Title

      Neurogenetics.

      Volume: 13 Issue: 4 Pages: 327-332

    • DOI

      10.1007/s10048-012-0337-6

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia2012

    • Author(s)
      *Saitsu H et al.
    • Journal Title

      Epilepsia

      Volume: 53(8):1441-1449 Issue: 8 Pages: 1441-1449

    • DOI

      10.1111/j.1528-1167.2012.03548.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 次世代シーケンサーを用いた脊髄小脳変性症の疾患責任遺伝子単離.2012

    • Author(s)
      土井 宏
    • Journal Title

      横浜医学

      Volume: 63 Pages: 641-648

    • Related Report
      2012 Research-status Report
  • [Presentation] CBSと関連する遺伝子変異2013

    • Author(s)
      土井宏、田中章景
    • Organizer
      第54回日本神経学会学術大会(シンポジウム)
    • Place of Presentation
      国際フォーラム(東京)
    • Year and Date
      2013-05-29
    • Related Report
      2013 Final Research Report
  • [Presentation] CBSと関連する遺伝子変異2013

    • Author(s)
      土井 宏、田中章景
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      国際フォーラム(東京)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 劣性型脊髄小脳変性症・痙性対麻痺6例に対するエクソーム解析2013

    • Author(s)
      土井 宏、岸田日帯、東山雄一、松本直通、田中章景
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      国際フォーラム(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 劣性型脊髄小脳変性症・痙性対麻痺遺伝子診断に対するエクソーム解析の有用性

    • Author(s)
      土井 宏、他
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Related Report
      2012 Research-status Report
  • [Book] 内科学書改訂第8版、代謝性疾患2013

    • Author(s)
      土井宏、田中章景
    • Publisher
      中山書店
    • Related Report
      2013 Final Research Report
  • [Book] 内科学書改訂第8版2013

    • Author(s)
      土井 宏、田中章景
    • Publisher
      中山書店
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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