Whole exome sequencing in moyamoya disease

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26461549
• Research Institution: Yokohama City University
• Principal Investigator: 宮武 聡子 横浜市立大学, 附属病院, 講師 (50637890)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: もやもや病 / 全エキソーム解析

Outline of Annual Research Achievements

もやもや病は小児～若年成人に好発する進行性の脳主幹動脈閉塞症である。もやもや病の疾患感受性を高める遺伝子としてRNF213遺伝子が知られている。これまでの研究で本遺伝子のR4810K多型を有すると発症リスクがおよそ200倍上昇することを明らかにした。しかし発症には本多型以外に他の遺伝的要因の存在が強く疑われる。そこで①RNF213遺伝子以外の責任遺伝子同定、②RNF213と非動脈硬化性の主幹動脈狭窄・閉塞症との関連、について解析を継続した。①については患者とその両親の全エキソーム解析を計64家系（36家系でトリ解析）で行った。遺伝形式を考慮した責任遺伝子の探索を継続している。②は典型もやもや病、片側もやもや病、類もやもや病、がその周辺の病態として知られており、RNF213遺伝子の R4810K多型との関連について検討した。これまで、もやもや病266例、片側もやもや病22例、類もやもや病17例、特定部位を外れた脳主幹動脈の閉塞6例を集積して同多型の解析を行った。もやもや病＞特定部位を外れた脳主幹動脈の閉塞症＞片側もやもや病＞類もやもや病という勾配をもった関連が統計学的に有意にみられることを確認した。

Research Products

• [Journal Article] Biallelic mutations in the myopalladin gene, MYPN are associated with childhood-onset, slowly progressive nemaline myopathy. (2017)
  • Author(s): Miyatake S, Mitsuhashi S, Hayashi YK, Purevjav E, Nishikawa A, Koshimizu E, Suzuki M, Yatabe K, Tanaka Y, Ogata K, Kuru S, Shiina M, Tsurusaki Y, Nakashima M, Mizuguchi T, Miyake N, Saitsu H, Ogata K, Kawai M, Towbin J, Nonaka I, Nishino I, Matsumoto N.
  • Journal Title: Am J Hum Genet Volume: 100 Pages: 169-178
  • DOI: 10.1016/j.ajhg.2016.11.017.
  • Acknowledgement Compliant
• [Journal Article] MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment. (2017)
  • Author(s): Satake T, Yamashita K, Hayashi K, Miyatake S, Tamura-Nakano M, Doi H, Furuta Y, Shioi G, Miura E, Takeo YH, Yoshida K, Yahikozawa H, Matsumoto N, Yuzaki M, Suzuki A.
  • Journal Title: EMBO J. Volume: 9 Pages: 1227-1242
  • DOI: 10.15252/embj.201695630.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin-Siris-like syndrome. (2017)
  • Author(s): Miyatake S, Okamoto N, Stark Z, Nabetani M, Tsurusaki Y, Nakashima M, Miyake N, Mizuguchi T, Ohtake A, Saitsu H, Matsumoto N.
  • Journal Title: J Hum Genet. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1038/jhg.2017.24.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. (2017)
  • Author(s): Imagawa E, Higashimoto K, Sakai Y, Numakura C, Okamoto N, Matsunaga S, Ryo A, Sato Y, Sanefuji M, Ihara K, Takada Y, Nishimura G, Saitsu H, Mizuguchi T, Miyatake S, Nakashima M, Miyake N, Soejima H, Matsumoto N.
  • Journal Title: Hum Mutat. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1002/humu.23200
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts. (2017)
  • Author(s): Iwama K, Mizuguchi T, Takanashi JI, Shibayama H, Shichiji M, Ito S, Oguni H, Yamamoto T, Sekine A, Nagamine S, Ikeda Y, Nishida H, Kumada S, Yoshida T, Awaya T, Tanaka R, Chikuchi R, Niwa H, Oka YI, Miyatake S, Nakashima M, Takata A, et al.
  • Journal Title: Clin Genet. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1111/cge.12991.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder. (2017)
  • Author(s): Mizuguchi T, Nakashima M, Kato M, Yamada K, Okanishi T, Ekhilevitch N, Mandel H, Eran A, Toyono M, Sawaishi Y, Motoi H, Shiina M, Ogata K, Miyatake S, Miyake N, Saitsu H, Matsumoto N.
  • Journal Title: J Hum Genet. Volume: 62 Pages: 525-529
  • DOI: 10.1038/jhg.2016.163.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A severe pulmonary complication in a patient with COL4A1-related disorder: A case report. (2017)
  • Author(s): Abe Y, Matsuduka A, Okanari K, Miyahara H, Kato M, Miyatake S, Saitsu H, Matsumoto N, Tomoki M, Ihara K.
  • Journal Title: Eur J Med Genet. Volume: 60 Pages: 169-17
  • DOI: 10.1016/j.ejmg.2016.12.008.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy (2016)
  • Author(s): Miyake N, Fukai R, Ohba C, Chihara T, Miura M, Shimizu H, Kakita A, Imagawa E, Shiina M, Ogata K, Okuno-Yuguchi J, Fueki N, Ogiso Y, Suzumura H, Watabe Y, Imataka G, Leong HY, Fattal-Valevski A, Kramer U, Miyatake S, Kato M, Okamoto N, et al.
  • Journal Title: Am J Hum Genet Volume: 99 Pages: 950-961
  • DOI: 10.1016/j.ajhg.2016.08.005.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia (2016)
  • Author(s): Makrythanasis P, Kato M, Zaki MS, Saitsu H, Nakamura K, Santoni FA, Miyatake S, Nakashima M, Issa MY, Guipponi M, Letourneau A, Logan CV, Roberts N, Parry DA, Johnson CA, Matsumoto N, Hamamy H, Sheridan E, Kinoshita T, Antonarakis SE, Murakami Y.
  • Journal Title: Am J Hum Genet Volume: 98 Pages: 615-626
  • DOI: J Neurol Neurosurg Psychiatry.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay. (2016)
  • Author(s): Saitsu H, Watanabe M, Akita T, Ohba C, Sugai K, Ong WP, Shiraishi H, Yuasa S, Matsumoto H, Beng KT, Saitoh S, Miyatake S, Nakashima M, Miyake N, Kato M, Fukuda A, Matsumoto N.
  • Journal Title: Sci Rep. Volume: 6 Pages: -
  • DOI: 10.1038/srep30072.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical features of SMARCA2 duplication overlap with Coffin-Siris syndrome. (2016)
  • Author(s): Miyake N, Abdel-Salam G, Yamagata T, Eid MM, Osaka H, Okamoto N, Mohamed AM, Ikeda T, Afifi HH, Piard J, van Maldergem L, Mizuguchi T, Miyatake S, Tsurusaki Y, Matsumoto N.
  • Journal Title: Am J Med Genet A. Volume: 170 Pages: 2662-70
  • DOI: 10.1002/ajmg.a.37778.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Somatic mutations in GLI3 and OFD1 involved in sonic hedgehog signaling cause hypothalamic hamartoma. (2016)
  • Author(s): Saitsu H, Sonoda M, Higashijima T, Shirozu H, Masuda H, Tohyama J, Kato M, Nakashima M, Tsurusaki Y, Mizuguchi T, Miyatake S, Miyake N, Kameyama S, Matsumoto N.
  • Journal Title: Ann Clin Transl Neurol. Volume: 3 Pages: 356-65
  • DOI: 10.1002/acn3.300.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Vein of Galen Aneurysmal Malformation in Monozygotic Twin. (2016)
  • Author(s): Komiyama M, Miyatake S, Terada A, Ishiguro T, Ichiba H, Matsumoto N.
  • Journal Title: World Neurosurg. Volume: 91 Pages: e11-5
  • DOI: 10.1016/j.wneu.2016.04.031
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Whole exome sequencing in congenital myopathy (2017)
  • Author(s): Satoko Miyatake
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2017-03-28 – 2017-03-30
  • Invited
• [Presentation] Atypical giant axonal neuropathy arising from a homozygous mutation by uniparental isodisomy (2016)
  • Author(s): Satoko Miyatake, Hiroko Tada, Jun-ichi Takanashi, Yoshiko Hirano, Masaharu Hayashi, Yasushi Oya, Naomichi Matsumoto, and Hirotomo Saitsu
  • Organizer: 第57回神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-05-18 – 2016-05-21
• [Presentation] Broadening of ANKRD11-related syndrome (2016)
  • Author(s): Satoko Miyatake, Nobuhiko Okamoto, Zornitza Stark, Yoshinori Tsurusaki, Mitsuko Nakashima, Hirotomo Saitsu, Noriko Miyake, Akira Ohtake, and Naomichi Matsumoto
  • Organizer: The13th International Congress og Human Genetics
  • Place of Presentation: Kyoto International Conference Center（京都府京都市）
  • Year and Date: 2016-04-03 – 2016-04-07
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] ネマリンミオパチーの確定診断法 (2016)
  • Inventor(s): 宮武聡子、松本直通
  • Industrial Property Rights Holder: 宮武聡子、松本直通
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-236425
  • Filing Date: 2016-12-06