Identification of pathogenic genes for genetic diseases using next-generation sequencing and high-density microarray

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659513
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: MATSUBARA Yoichi 東北大学, 大学院・医学系研究科, 教授 (00209602)
• Co-Investigator(Kenkyū-buntansha): NIIHORI Tetsuya 東北大学, 大学院・医学系研究科, 助教 (40436134) ; KURE Shigeo 東北大学, 大学院・医学系研究科, 教授 (10205221)
• Research Collaborator: AOKI Yoko 東北大学, 大学院・医学系研究科, 准教授 (80332500)
• Project Period (FY): 2011 – 2012
• Keywords: 遺伝性疾患 / 遺伝子解析 / シークエンス

Research Abstract

Next-generation sequencing and high-density microarray analysis were used to investigate disease-causing genes for genetic diseases in which molecular pathogenesis had not been clarified. We successfully identified a pathogenic gene for a subtype of myopathies in one family. We also identified novel disease-causing genes in a congenital anomaly syndrome and an endocrine disorder. The results would lead to the understanding of the pathogenesis of these disorders and the development of therapeutic means.

Research Products

• [Journal Article] Exome sequencing identifies a novel TTN mutation in a family with myofibrillar myopathy with early respiratory failure (2013)
  • Author(s): Izumi R, Niihori T, Suzuki N, Kato M, Warita H, Tateyama M, Aoki M, TakahashiT, Nagashima T, Funayama R, Nakayama N, Abe K, Matsubara Y
  • Journal Title: J Hum Genet Volume: 58(5) Pages: 259-66
  • DOI: doi:10.1038/jhg.2013.9
  • Peer Reviewed
• [Journal Article] A young man with progressive subcortical lesions and optic nerve atrophy (2012)
  • Author(s): Komatsuzaki S, Sakamoto O, Fuse N, Uematsu M, Matsubara Y, Ohura T. Clinical Reasoning
  • Journal Title: Neurology Volume: 79(7) Pages: e63-68
  • DOI: doi:10.1212/WNL.0b013e3182648bb6
  • Peer Reviewed
• [Journal Article] Casitas B-cell lymphoma mutation in childhood T-cell acute lymphoblastic leukemia (2012)
  • Author(s): Saito Y, Aoki Y, Muramatsu H, Makishima H, Maciejewski JP, Imaizumi M, Rikiishi T, Sasahara Y, Kure S, NiihoriT, Tsuchiya S, Kojima S, Matsubara Y
  • Journal Title: Leuk Res Volume: 36(8) Pages: 1009-1015
  • DOI: doi:10.1016/j.leukres.2012.04.018
  • Peer Reviewed
• [Journal Article] BOSHI Study Group. Daily serial hemodynamic data during pregnancy and seasonal variation: theBOSHI study (2012)
  • Author(s): Metoki H, Ohkubo T, Obara T, Akutsu K, Yamamoto M, Ishikuro M, Sakurai K, Iwama N, Katagiri M, Sugawara J, Hirose T, Sato M, Kikuya M, Yagihashi K, Matsubara Y, Yaegashi N, Mori S, Suzuki M, Imai Y
  • Journal Title: Clin Exp Hypertens Volume: 34(4) Pages: 290-296
  • DOI: doi:10.3109/10641963.2012.681086
  • Peer Reviewed
• [Journal Article] Costello and CFC syndrome study group in Japan. Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan: findings from a nationwide epidemiological survey (2012)
  • Author(s): Abe Y, Aoki Y, Kuriyama S, Kawame H, Okamoto N, Kurosawa K, Ohashi H, Mizuno S, Ogata T, Kure S, Niihori T, Matsubara Y
  • Journal Title: Am J Med GenetA Volume: 158A(5) Pages: 1083-1094
  • Peer Reviewed
• [Journal Article] Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease (2012)
  • Author(s): Miyatake S, Miyake N, Touho H, Nishimura-Tadaki 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, Matsubara Y, Kure S, Matsumoto N
  • Journal Title: Neurology Volume: 78(11) Pages: 803-810
  • DOI: doi:10.1212/WNL.0b013e318249f71f
  • Peer Reviewed
• [Journal Article] Simple and rapid genetic testing for citrin deficiency by screening 11 prevalent mutations in SLC25A13 (2012)
  • Author(s): Kikuchi A, Arai-Ichinoi N, Sakamoto O, Matsubara Y, Saheki T, Kobayashi K, Ohura T, Kure S
  • Journal Title: Mol Genet Metab Volume: 105(4) Pages: 553-558
  • DOI: doi:10.1016/j.ymgme.2011.12.024
  • Peer Reviewed
• [Journal Article] Mutations in genes encoding theglycine cleavage system predispose to neural tube defects in mice and humans (2012)
  • Author(s): Narisawa A, Komatsuzaki S, Kikuchi A, Niihori T, Aoki Y, Fujiwara K, Tanemura M, Hata A, Suzuki Y, Relton CL, Grinham J, Leung KY, Partridge D, Robinson A, Stone V, Gustavsson P, Stanier P, Copp AJ, Greene ND, Tominaga T, Matsubara Y, Kure S
  • Journal Title: Hum Mol Genet Volume: 21(7) Pages: 1496-1503
  • DOI: doi:10.1093/hmg/ddr585
  • Peer Reviewed
• [Journal Article] A Case of Almost Unilateral Focal Dermal Hypoplasia Resulting From a Novel Mutation in the Gene (2012)
  • Author(s): Asano M, Fujimura T, Wakusawa C, Aoki Y, Matsubara Y, Aiba S
  • Journal Title: Acta Derm Venereol Volume: 93(1) Pages: 120-121
  • DOI: doi:10.2340/00015555-1399
  • Peer Reviewed
• [Journal Article] (International Confederation of Countries Advisory Council). Human variome project country nodes: Documenting genetic information within a country (2012)
  • Author(s): Patrinos GP, Smith TD, Howard H, Al-Mulla F, Chouchane L, Hadjisavvas A, Hamed SA, Li XT, Marafie M, Ramesar RS, Ramos FJ, de Ravel T, El-Ruby MO, Shrestha TR, Sobrido MJ, Tadmouri G, Witsch-Baumgartner M, Zilfalil BA, Auerbach AD, Carpenter K, Cutting GR, Dung VC, Grody W, Hasler J, Jorde L, Kaput J, Macek M, Matsubara Y, Padilla C, Robinson H, Rojas-Martinez A, Taylor GR, Vihinen M, Weber T, Burn J, Qi M, Cotton RG, Rimoin D
  • Journal Title: Hum Mutat Volume: 33(11) Pages: 1513-1519
  • DOI: doi:10.1002/humu.22147
  • Peer Reviewed
• [Journal Article] Implantable cardioverter defibrillator for progressive hypertrophic cardiomyopathy in a patient with LEOPARD syndrome and a novel PTPN11 mutation Gln510His (2011)
  • Author(s): Wakabayashi Y, Yamazaki K, Narumi Y, Fuseya S, Horigome M, Wakui K,Fukushima Y, Matsubara Y, Aoki Y, Kosho T
  • Journal Title: Am J Med Genet A Volume: 155A(10) Pages: 2529-2533
  • DOI: doi:10.1002/ajmg.a.34194
  • Peer Reviewed
• [Journal Article] HRAS mutants identified in Costello syndrome patients can induce cellular senescence: possible implications for the pathogenesis of Costello syndrome (2011)
  • Author(s): Niihori T, Aoki Y, Okamoto N, Kurosawa K, Ohashi H, Mizuno S, Kawame H, Inazawa J, Ohura T, Arai H, Nabatame S,Kikuchi K, Kuroki Y, Miura M, Tanaka T, Ohtake A, Omori I, Ihara K, Mabe H, Watanabe K, Niijima S, Okano E, Numabe H, Matsubara Y
  • Journal Title: J Hum Genet Volume: 56(10) Pages: 707-715
  • DOI: doi:10.1038/jhg.2011.85
  • Peer Reviewed
• [Journal Article] Association between cancer risk anddrug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan (2011)
  • Author(s): Tamaki Y, Arai T, Sugimura H, Sasaki T, Honda M, Muroi Y, Matsubara Y, Kanno S, Ishikawa M, Hirasawa N, Hiratsuka M
  • Journal Title: Drug Metab Pharmacokinet Volume: 26(5) Pages: 516-522
  • Peer Reviewed
• [Journal Article] Functional characterization of CYP2B6 allelic variants in demethylation of antimalarial artemether (2011)
  • Author(s): Honda M, Muroi Y, Tamaki Y, Saigusa D, Suzuki N, Tomioka Y, Matsubara Y, Oda A, Hirasawa N, Hiratsuka M
  • Journal Title: Drug Metab Dispos Volume: 39(10) Pages: 1860-1865
  • Peer Reviewed
• [Journal Article] Novel single nucleotide polymorphism of the CYP2A13 gene in Japanese individuals (2011)
  • Author(s): Tamaki Y, Honda M, Muroi Y, Arai T, Sugimura H, Matsubara Y, Kanno S, Ishikawa M, Hirasawa N, Hiratsuka M
  • Journal Title: Drug Metab Pharmacokinet Volume: 26(5) Pages: 544-547
  • Peer Reviewed
• [Journal Article] Implications of prenatal diagnosis of the fetus with both interstitial deletion and a small marker ring originating from chromosome 5 (2011)
  • Author(s): Ohashi H, Suzumori K, Chisaka Y, Sonta S, Kobayashi T, Aoki Y, Matsubara Y, Sone M, Shaffer LG
  • Journal Title: Am J Med Genet A Volume: 155A(1) Pages: 192-196
  • DOI: doi:10.1002/ajmg.a.33764
  • Peer Reviewed
• [Journal Article] Afamilial case of LEOPARD syndrome associated with a high-functioning autism spectrum disorder (2011)
  • Author(s): Watanabe Y, Yano S, Niihori T, Aoki Y, Matsubara Y, Yoshino M, Matsuishi T
  • Journal Title: Brain Dev Volume: 33(7) Pages: 576-579
  • DOI: doi:10.1016/j.braindev.2010.10.006
  • Peer Reviewed
• [Journal Article] A genome-wide association study identifies RNF213 as the first Moyamoya disease gene (2011)
  • Author(s): Kamada F, Aoki Y, Narisawa A, Abe Y,Komatsuzaki S, Kikuchi A, Kanno J, Niihori T, Ono M, Ishii N, Owada Y, Fujimura M, Mashimo Y, Suzuki Y, Hata A, Tsuchiya S, Tominaga T, Matsubara Y, Kure S
  • Journal Title: J Hum Genet Volume: 56(1) Pages: 34-40
  • DOI: doi:10.1038/jhg.2010.132
  • Peer Reviewed
• [Journal Article] Cardio-facio-cutaneous syndrome with infantile spasms and delayed myelination (2011)
  • Author(s): Aizaki K, Sugai K, Saito Y, Nakagawa E, Sasaki M, Aoki Y, Matsubara Y
  • Journal Title: Brain Dev Volume: 33(2) Pages: 166-169
  • DOI: doi:10.1016/j.braindev.2010.03.008.
  • Peer Reviewed
• [Presentation] Noonan症候群類縁疾患と小児血液腫瘍におけるCBLの分子遺伝学的解析 (2012)
  • Author(s): 齋藤由佳、青木洋子、村松秀樹、今泉益栄、力石健、笹原洋二、呉繁夫、新堀哲也、小島勢二、松原洋一
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 東京
  • Year and Date: 20121024-27
• [Presentation] Epidemiological features of Costello syndrome and cardio-facio-cutaneous syndrome: findings from the first nationwide survey (2011)
  • Author(s): Y. Abe, Y. Aoki, S. Kuriyama, H. Kawame, N. Okamoto, K. Kurosawa, H. Ohashi, S. Mizuno, T. Ogata, S. Kure, T. Niihori, Y. Matsubara
  • Organizer: 12th International Congress of Human Genetics
  • Place of Presentation: モントリオール、カナダ
  • Year and Date: 20111011-15
• [Presentation] Identification of a susceptibility gene for Moyamoya disease, RNF213 by a genome-wide association study (2011)
  • Author(s): S. Kure, F. Kamada, Y. Aoki ,Y. Abe S, Komatsuzaki, A. Kikuch, J.Kanno, T. Niihori, M. Fuji-mura,Y. Mashimo, M. Ono, N. Ishii, Y. Owada, Y. Suzuki, A. Hata,T. Tominaga, Y. Matsubara
  • Organizer: 12th International Congress of Human Genetics
  • Place of Presentation: モントリオール、カナダ
  • Year and Date: 20111011-15