Isolation of causative genes for recessive spinocerebellar ataxia

• Project/Area Number: 22790823
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: DOI Hiroshi 横浜市立大学, 医学部, 助教 (10326035)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 脊髄小脳変性症 / エクソーム / 常染色体劣性遺伝 / 劣性遺伝 / 次世代シーケンサー

Research Abstract

Autosomal recessive cerebellar ataxias(ARCAs) are heterogeneous disorders clinically associated with cerebellar ataxias. In this study, we performed the whole exome sequencing analysis combined with homozygosity mapping and linkage analysis, to identify causative mutations from three Japanese families of ARCA. As a result, a homozygous missense mutation in SYT14, encoding synaptotagmin XIV, was identified in one of the families. We showed that the above methods could successfully identify a causative mutation from small family.

Research Products

• [Journal Article] Exome sequencing in a family with an X-linked lethal malformation syndrome : clinical consequences of hemizygous truncating OFD1 mutations in male patients (2012)
  • Author(s): Tsurusaki Y, Kosho T, Hatasaki K, Narumi Y, Wakui K, Fukushima Y, Doi H, Saitsu H, Miyake N, Matsumoto N
  • Journal Title: Clin Genet Volume: (in press) Issue: 2 Pages: 135-144
  • DOI: 10.1111/j.1399-0004.2012.01885.x
  • Peer Reviewed
• [Journal Article] Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome (2012)
  • Author(s): Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N
  • Journal Title: Nat Genet Volume: 44 Issue: 4 Pages: 376-378
  • DOI: 10.1038/ng.2219
  • Peer Reviewed
• [Journal Article] Homozygous c. 14576G> A Variant of<I> RNF213</I> Predicts Early-Onset and Severe Form of Moyamoya Disease (2012)
  • Author(s): Miyatake S, Miyake N, Touho H, Nishimura-T, A, Kondo Y, Okada ; I, Tsurusaki ; Y, Doi H, Sakai H, Saitsu ; H, Shimojima K, Yamamoto T, Higurashi M, Kawahara, N, Kawauchi, H, Nagasaka, K, Okamoto N, Mori, T, Koyano S, Kuroiwa Y, Taguri M, Morita S, Matsuba S, Kure S, Matsumoto N
  • Journal Title: Neurology Volume: 78(11) Issue: 11 Pages: 803-10
  • DOI: 10.1212/wnl.0b013e318249f71f
  • Peer Reviewed
• [Journal Article] Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features (2012)
  • Author(s): Yoneda Y, Saitsu H, Touyama M, Makita Y, Miyamoto A, Hamada K, Kurotaki N, Tomita H, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Ogata K, Naritomi K, Matsumoto N
  • Journal Title: J Hum Genet Volume: 57巻 Issue: 3 Pages: 207-211
  • DOI: 10.1038/jhg.2012.7
  • NAID: 10030712151
  • Peer Reviewed
• [Journal Article] A family of oculofaciocardiodental syndrome(OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS (2012)
  • Author(s): Kondo Y, Saitsu H, Miyamoto T, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Ryoo NK, Kim JH, Yu YS, Matsumoto N
  • Journal Title: J Hum Genet Volume: 57巻 Issue: 3 Pages: 197-201
  • DOI: 10.1038/jhg.2012.4
  • NAID: 10030712110
  • Peer Reviewed
• [Journal Article] Association of genomic deletions in the STXBP1 gene with Ohtahara syndrome (2012)
  • Author(s): *Saitsu H et al.
  • Journal Title: Clinical Genetics Volume: 81(4):399-402 Issue: 4 Pages: 86-90
  • DOI: 10.1111/j.1399-0004.2011.01733.x
  • Peer Reviewed
• [Journal Article] Rapid detection of gene mutations responsible for non-syndromic aortic aneurysm and dissection using two different methods : resequencing microarray technology and next-generation sequencing (2012)
  • Author(s): Sakai H, Suzuki S, Mizuguchi T, Imoto K, Yamashita Y, Doi H, Kikuchi M, Tsurusaki Y, Saitsu H, Miyake N, Masuda M, Matsumoto N
  • Journal Title: Hum Genet Volume: 131巻 Issue: 4 Pages: 591-599
  • DOI: 10.1007/s00439-011-1105-7
  • Peer Reviewed
• [Journal Article] A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5 (2012)
  • Author(s): *Saitsu H et al.
  • Journal Title: Brain Dev Volume: 34(5):364-7 Issue: 5 Pages: 364-367
  • DOI: 10.1016/j.braindev.2011.07.004
  • NAID: 10031050724
  • Peer Reviewed
• [Journal Article] De Novo and Inherited Mutations in COL4A2, Encoding the Type IV Collagen alpha2 Chain Cause Porencephaly (2011)
  • Author(s): Yoneda Y, et al.
  • Journal Title: Am J Hum Genet Volume: 90 Issue: 1 Pages: 86-90
  • DOI: 10.1016/j.ajhg.2011.11.016
  • Peer Reviewed
• [Journal Article] Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation (2011)
  • Author(s): Doi H, Yoshida K, Yasuda T, Fukuda M, Fukuda Y, Morita H, et al
  • Journal Title: Am J Hum Genet Volume: 89 Issue: 2 Pages: 320-327
  • DOI: 10.1016/j.ajhg.2011.07.012
  • Peer Reviewed
• [Journal Article] Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2) (2011)
  • Author(s): Saitsu H, Osaka H, Sugiyama S, Kurosawa K, Mizuguchi T, Nishiyama K, Nishimura A, Tsurusaki Y, Doi H, Miyake N, Harada N, Kato M, Matsumoto N
  • Journal Title: Am J Med Genet A Volume: (in press) Issue: 1 Pages: 2879-84
  • DOI: 10.1002/ajmg.a.34363
  • Peer Reviewed
• [Journal Article] Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. (2011)
  • Author(s): Saitsu H. et al.
  • Journal Title: Am J Hum Genet. Volume: 89 Issue: 5 Pages: 644-651
  • DOI: 10.1016/j.ajhg.2011.10.003
  • Peer Reviewed
• [Journal Article] A novel homozygous mutation of DARS2 may cause a severe LBSL variant (2011)
  • Author(s): Miyake N, Yamashita S, Kurosawa K, Miyatake S, Tsurusaki Y, Doi H, Saitsu H, Matsumoto N
  • Journal Title: Clin Genet Volume: 80巻 Issue: 3 Pages: 293-296
  • DOI: 10.1111/j.1399-0004.2011.01644.x
  • Peer Reviewed
• [Journal Article] Exome sequencing of two patients in a family with atypical X-linked leukodystrophy (2011)
  • Author(s): Tsurusaki Y, Okamoto N, Suzuki Y, Doi H, Saitsu H, Miyake N, Matsumoto N
  • Journal Title: Clin Genet Volume: 80巻 Issue: 2 Pages: 161-166
  • DOI: 10.1111/j.1399-0004.2011.01721.x
  • Peer Reviewed
• [Journal Article] Exonic deletion of CASP10 in a patient presenting with systemic juvenile idiopathic arthritis, but not with autoimmune lymphoproliferative syndrome type IIa (2011)
  • Author(s): Tadaki H, Saitsu H, Kanegane H, Miyake N, Imagawa T, Kikuchi M, Hara R, Kaneko U, Kishi T, Miyamae T, Nishimura A, Doi H, Tsurusaki Y, Sakai H, Yokota S, Matsumoto N
  • Journal Title: Int J Immunogenet Volume: 38巻 Issue: 4 Pages: 287-293
  • DOI: 10.1111/j.1744-313x.2011.01005.x
  • Peer Reviewed
• [Journal Article] De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis (2011)
  • Author(s): Tadaki H, Saitsu H, Nishimura-Tadaki A, Imagawa T, Kikuchi M, Hara R, Kaneko U, Kishi T, Miyamae T, Miyake N, Doi H, Tsurusaki Y, Sakai H, Yokota S, Matsumoto N
  • Journal Title: J Hum Genet Volume: 56巻 Issue: 5 Pages: 343-347
  • DOI: 10.1038/jhg.2011.16
  • NAID: 10030659126
  • Peer Reviewed
• [Journal Article] Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing (2011)
  • Author(s): Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N
  • Journal Title: J Med Genet Volume: 48巻 Issue: 9 Pages: 606-609
  • DOI: 10.1136/jmg.2010.083535
  • Peer Reviewed
• [Journal Article] Breakpoint determination of X ; autosome balanced translocations in four patients with premature ovarian failure. (2011)
  • Author(s): 只木章, 他
  • Journal Title: Journal of Human Genetics Volume: 56 Pages: 156-160
  • Peer Reviewed
• [Journal Article] A de novo deletion of 20q11.2-q12 in a boy presenting with abnormal hands and feet, retinal dysplasia, and intractable feeding difficulty. (2011)
  • Author(s): 平木洋子, 他
  • Journal Title: American Journal of Medical Genetics Part A Volume: 155 Pages: 409-14
  • Peer Reviewed
• [Journal Article] De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis. (2011)
  • Author(s): 只木弘美, 他
  • Journal Title: Journal of Human Genetics Volume: (In press)
  • Peer Reviewed
• [Journal Article] Exonic deletion of CASP10 in a patient presenting with systemic juvenile idiopathic arthritis, but not with autoimmune lymphoproliferative syndrome type IIa. (2011)
  • Author(s): 只木弘美, 他
  • Journal Title: International Journal of Immunogenetics Volume: (In press)
  • Peer Reviewed
• [Journal Article] Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing. (2011)
  • Author(s): 鶴崎美徳, 他
  • Journal Title: Journal of Medical Genetics Volume: (In press)
  • Peer Reviewed
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome. (2010)
  • Author(s): 三宅紀子, 他
  • Journal Title: Human Mutation Volume: 31 Pages: 966-974
  • Peer Reviewed
• [Journal Article] Paternal mosaicism of an STXBP1 mutation in OS. (2010)
  • Author(s): 才津浩智, 他
  • Journal Title: Clinical Genetics Volume: (In press)
  • Peer Reviewed
• [Journal Article] SMOC1 is essential for ocular and limb development in humans and mice. (2010)
  • Author(s): 岡田一平, 他
  • Journal Title: The American Journal of Human Genetics Volume: 88 Pages: 30-41
  • Peer Reviewed
• [Presentation] Exome sequencing reveals a novel homozygous mutation in adult-onset autosomal recessive spinocerebellar ataxia with psychomotor retardation (2011)
  • Author(s): 土井宏
  • Organizer: American Society of Human Genetics Annual Meeting
  • Place of Presentation: Montreal、Canada
  • Year and Date: 2011-10-14
• [Presentation] Exome sequencing reveals a novel homozygous mutation in adult-onset autosomal recessive spinocerebellar ataxia with psychomotor retardation (2011)
  • Author(s): 土井宏
  • Organizer: American Society of Human Genetics Annual Meeting 2011
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2011-10-14
• [Presentation] 次世代シーケンサーを用いた常染色体劣性遺伝性脊髄小脳変性症責任遺伝子の単離研究 (2011)
  • Author(s): 土井宏
  • Organizer: 日本神経学会学術大会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-05-19
• [Presentation] 脊髄小脳失調症2型患者脊髄前角細胞の免疫組織化学的検討 (2010)
  • Author(s): 土井宏, 他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京、東京国際フォーラム
  • Year and Date: 2010-05-21
• [Patent(Industrial Property Rights)] 常染色体劣性遺伝性脊髄小脳変性症の検出方法 (2011)
  • Inventor(s): 土井宏、松本直通
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 2011-136277
  • Filing Date: 2011-06-20