Exome analysis of spinocerebellar ataxias

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790893
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Yokohama 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
• 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.

Research Products

• [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 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(14) Pages: 1629-1633
  • Peer Reviewed
• [Journal Article] Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy (2013)
  • 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
  • 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(1) Pages: 151-3
  • Peer Reviewed
• [Journal Article] A novel SCARB2 mutation causing late-onset progressive myoclonus epilepsy (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Phenotypic spectrum of COL4A1 mutations : porencephaly to schizencephaly (2013)
  • 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
  • Peer Reviewed
• [Journal Article] The diagnostic utility of exome sequencing in Joubert syndrome and related disorders (2013)
  • 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
  • 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, 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
  • Peer Reviewed
• [Journal Article] Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome (2012)
  • 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
  • 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
  • Peer Reviewed
• [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
• [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
  • Total Pages: 361-374
  • Publisher: 中山書店