Whole exome sequencing in moyamoya disease

• Project/Area Number: 26461549
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yokohama City University
• Principal Investigator: MIYATAKE Satoko 横浜市立大学, 附属病院, 講師 (50637890)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: もやもや病 / エキソーム解析 / 全エキソーム解析 / RNF213

Outline of Final Research Achievements

Moyamoya disease is a cerebrovascular disease characterized by progressive occlusion of the terminal portion of the carotid arteries and their branches, bilaterally. The p.R4810K variant in RNF213 gene is known to be associated with moyamoya disease, but it is assumed that there may be other genetic factors contributing its onset. We performed whole exome sequencing on 65 pedigrees with moyamoya disease, searching for the mutated gene in this cohort. Two patients had pathogenic mutation in genes associated with specific syndromes, in which moyamoya disease had not been known as their clinical symptom. We found that p.R4810K variant in RNF213 gene is significantly associated with not only moyamoya disease but also unilateral moyamoya disease, akin-moyamoya disease, and moyamoya-like disease in which different portion of carotid arteries are stenotic/occlusive.

Research Products

• [Journal Article] Biallelic mutations in MYPN, encoding Myopalladin, 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: American Journal of Human Genetics Volume: 100 Issue: 1 Pages: 169-178
  • DOI: 10.1016/j.ajhg.2016.11.017
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biallelic TBCD mutations cause early-onset neurodegenerative encephalopathy (2017)
  • Author(s): Miyake N, Fukai R, Ohba C, ... 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, Sato Y, Mitsuhashi S, Nishino I, Kaneko N, Nishiyama A, Tamura T, Mizuguchi T, Nakashima M, Tanaka F, Saitsu H, Matsumoto N
  • Journal Title: American Journal of Human Genetics Volume: 99 Issue: 4 Pages: 950-961
  • DOI: 10.1016/j.ajhg.2016.08.005
  • Peer Reviewed / Open Access / Int'l Joint Research / 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: EMBOJ Volume: 36 Issue: 9 Pages: 1227-1242
  • DOI: 10.15252/embj.201695630
  • Peer Reviewed / Open Access / 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 Issue: 8 Pages: 741-746
  • DOI: 10.1038/jhg.2017.24
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome (2017)
  • Author(s): Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
  • Journal Title: Human Mutation Volume: 印刷中 Issue: 6 Pages: 637-648
  • DOI: 10.1002/humu.23200
  • Peer Reviewed / Open Access / Int'l Joint Research / 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, Miyake N, Ito S, Saitsu H, Matsumoto N.
  • Journal Title: Clinical Genetics Volume: - Issue: 2 Pages: 180-187
  • 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: Journal of Human Genetics Volume: 62 Issue: 5 Pages: 525-529
  • DOI: 10.1038/jhg.2016.163
  • NAID: 40021210259
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A severe pulmonary complication in a patient with COL4A1-related disorder (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 Issue: 3 Pages: 169-171
  • DOI: 10.1016/j.ejmg.2016.12.008
  • Peer Reviewed
• [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
  • 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. and Matsumoto N.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 30072-30072
  • DOI: 10.1038/srep30072
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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 Issue: 10 Pages: 2662-2670
  • DOI: 10.1002/ajmg.a.37778
  • Peer Reviewed / Int'l Joint Research / 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: 24 Issue: 5 Pages: 356-65
  • DOI: 10.1002/acn3.300
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vein of Galen Aneurysmal malformation in monozygotic twin (2016)
  • Author(s): Komiyama M, Miyatake M Watanabe Y, Terada A, Ishiguro T, Ichiba H, Matsumoto M
  • Journal Title: World Neurosurg Volume: 91:672 Pages: 672.e11-672.e15
  • DOI: 10.1016/j.wneu.2016.04.031
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Detecting copy number variations in whole exome sequencing data using exome hidden markov model - an expectation of “exome-first” approach. (2015)
  • Author(s): Miyatake S, Koshimizu E, Fujita A, Fukai R, Imagawa E, Ohba C, Kuki I, Makita Y, Ogata T, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N
  • Journal Title: J Hum Genet Volume: 1 Issue: 4 Pages: 124-124
  • DOI: 10.1038/jhg.2014.124
  • Peer Reviewed / Open Access
• [Journal Article] Biallelic mutations in nuclear pore complex subunit NUP107 cause early-childhood-onset steroid-resistant nephrotic syndrome (2015)
  • Author(s): Miyake N, Tsukaguchi H, Koshimizu E, Shono A, Matsunaga S, Shiina M, Mimura Y, Imamura S, Hirose T, Okudela K, Nozu K, Akioka Y, Hattori M, Yoshikawa N, Kitamura A, Cheong HI, Kagami S, Yamashita M, Fujita A, Miyatake S, Tsurusaki Y, Nakashima M, Saitsu H, Ohashi K, Imamoto N, Ryo A, Ogata K, Iijima K, Matsumoto N
  • Journal Title: Am J Hum Genet Volume: 97(4) Issue: 4 Pages: 555-566
  • DOI: 10.1016/j.ajhg.2015.08.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance. (2015)
  • Author(s): Ohba, C., K. Haginoya, H. Osaka, K. Kubota, A. Ishiyama, T. Hiraide, H. Komaki, M. Sasaki, S. Miyatake, M. Nakashima, Y. Tsurusaki, N. Miyake, F. Tanaka, H. Saitsu, and N. Matsumoto
  • Journal Title: J Hum Genet Volume: 60 Issue: 12 Pages: 739-42
  • DOI: 10.1038/jhg.2015.108
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel mutation in ELOVL4 leading to spinocerebellar ataxia (SCA) with the hot cross bun sign but lacking erythrokeratodermia: a broadened spectrum of SCA34. (2015)
  • Author(s): Ozaki K, Doi H, Mitsui J, Sato N, Iikuni Y, Majima T, Yamane K, Irioka T, Ishiura H, Doi K, Morishita S, Higashi M, Sekiguchi T, Koyama K, Ueda N, Miura Y, Miyatake S, Matsumoto N, Yokota T, Tanaka F, Tsuji S, Mizusawa H, Ishikawa K.
  • Journal Title: JAMA Neurology Volume: 72 Issue: 7 Pages: 797-805
  • DOI: 10.1001/jamaneurol.2015.0610
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing. (2015)
  • Author(s): Saitsu, H., T. Akita, J. Tohyama, H. Goldberg-Stern, Y. Kobayashi, R. Cohen, M. Kato, C. Ohba, S. Miyatake, Y. Tsurusaki, M. Nakashima, N. Miyake, A. Fukuda, and N. Matsumoto
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 15199-15199
  • DOI: 10.1038/srep15199
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Predominant cerebellar phenotype in spastic paraplegia 7 (SPG7). (2015)
  • Author(s): Yahikozawa H, Yoshida K, Shunichi S, Hanyu N, Doi H, Miyatake S, Matsumoto N.
  • Journal Title: Human Genome Variation Volume: 2 Issue: 1 Pages: 15015-15015
  • DOI: 10.1038/hgv.2015.12
  • Peer Reviewed / Open Access
• [Journal Article] Atypical giant axonal neuropathy arising from a homozygous mutation by uniparental isodisomy (2014)
  • Author(s): Miyatake S, Koshimizu E, Tada H, Satoshi Moriya S, Takanashi J, Hirano Y, Hayashi M, Nakashima M, Tsurusaki Y, Miyake N, Matsumoto N, Saitsu H.
  • Journal Title: Clin Genet Volume: 87（4） Issue: 4 Pages: 395-397
  • DOI: 10.1111/cge.12455
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dominant mutations in ORAI1 cause tubular-aggregate-myopathy with hypocalcemia by constitutive activation of store-operated Ca2+ channel (2014)
  • Author(s): Endo Y, Noguchi S, Hara Y, Hayashi YK, Motomura K, Murakami N, Tanaka S, Yamashita S, Kizu R, Bamba M, Goto Y, Matsumoto N, Nonaka I, Nishino I.
  • Journal Title: Hum Mol Genet Volume: 24（3） Issue: 3 Pages: 637-648
  • DOI: 10.1093/hmg/ddu477
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ‘Cortical cerebellar atrophy’ dwindles away in the era of next-generation sequencing. (2014)
  • Author(s): Yoshida K, Miyatake S, Kinoshita T, Doi H, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N.
  • Journal Title: Journal of Human Genetics Volume: 59 Issue: 10 Pages: 589-590
  • DOI: 10.1038/jhg.2014.75
  • Peer Reviewed / Open Access
• [Journal Article] De novo SOX11 mutations cause Coffin-Siris syndrome (2014)
  • Author(s): Tsurusaki Y, Ohashi H, Phadke S, Koshimizu E, Kou I, Shiina M, Suzuki T, Okamoto N, Imamura S, Yamashita M, Watanabe S, Yoshiura K-i, Kodera H, Miyatake S, Nakashima N, Saitsu H, Ogata K, Ikegawa S, Miyake N, and Matsumoto N.
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 4011-4011
  • DOI: 10.1038/ncomms5011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expanding the phenotypic spectrum of TUBB4A-associated (2014)
  • Author(s): Miyatake S, Osaka H, Shiina M, Sasaki M, Takanashi J, Haginoya K, Wada T,
  • Journal Title: Neurology Volume: 82(24) Issue: 24 Pages: 2230-7
  • DOI: 10.1212/wnl.0000000000000535
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Deep sequencing detects very low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy (2014)
  • Author(s): Miyatake S, Koshimizu E, Hayashi YK, Miya K, Shiina M, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Ogata K, Nishino I, Matsumoto N.
  • Journal Title: Neuromuscul Disord Volume: 24（7） Issue: 7 Pages: 642-647
  • DOI: 10.1016/j.nmd.2014.04.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation (2014)
  • Author(s): Doi H, Ushiyama M, Baba T, Tani K, Shiina M, Ogata K, Miyatake S, Yuzawa YF, Tsuji S, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Ikeda S, Tanaka F, Matsumoto N, Yoshida K
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 7132-7132
  • DOI: 10.1038/srep07132
  • NAID: 120007100602
  • Peer Reviewed / Open Access
• [Journal Article] Clinical exome sequencing in neurology practice (2014)
  • Author(s): Miyatake S,Matsumoto N.
  • Journal Title: Nat Rev Neurol Volume: 10（12） Issue: 12 Pages: 676-678
  • DOI: 10.1038/nrneurol.2014.213
  • 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
  • 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
• [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
  • Int'l Joint Research
• [Presentation] 全エキソーム解析で8.9Mbの中間部欠失を同定した13q症候群の1例 (2015)
  • Author(s): 宮武聡子、橋本祐至、岡本伸彦、中島光子、才津浩智、三宅紀子、松本直通
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-15
• [Presentation] Detecting copy number variations by analyzing whole exome sequencing data using the eXome Hidden Markov Model. (2015)
  • Author(s): Miyatake S, Koshimizu E, Fujita A, Fukai R, Imagawa E, Ohba C, Kuki I, Araki A, Makita Y, Ogata T, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N
  • Organizer: American Society of Human Genetics 65th Annual Meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] TUBB4A変異によるミエリン低形成白質脳症・ジストニア (2015)
  • Author(s): 宮武聡子
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-05-21
  • Invited
• [Presentation] 全エキソーム解析で片親性イソダイソミーに起因するホモ接合性変異が同定できた巨大軸索ニューロパチー症例 (2014)
  • Author(s): 宮武聡子、多田弘子、守屋聡、高梨潤一、平野嘉子、林雅晴、大矢寧、中島光子、鶴崎美徳、三宅紀子、松本直通、才津浩智
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2014-11-20
• [Presentation] Expanding the phenotypic spectrum of TUBB4A-associated hypomyelinating leukoencephalopathies (2014)
  • Author(s): Satoko Miyatake, Hitoshi Osaka, Masaaki Shiina, Masayuki Sasaki, Jun-ichi Takanashi, Kazuhiro Haginoya, Takahito Wada, Masafumi Morimoto, Naoki Ando, Yoji Ikuta, Mitsuko Nakashima, Yoshinori Tsurusaki, Noriko Miyake, Kazuhiro Ogata, Naomichi Matsumoto, and Hirotomo Saitsu
  • Organizer: American Society Of Human Genetics 64th Annual Meeting
  • Place of Presentation: SanDiego, USA
  • Year and Date: 2014-10-20
• [Presentation] ネマリンミオパチーの新規原因遺伝子KLHL40の同定 (2014)
  • Author(s): 宮武聡子、林由起子、輿水江里子、Gianina Ravenscroft、三宅紀子、土井宏、鶴崎美徳、才津浩智、小坂仁、山下純正、大宅喬、増澤祐子、今村伸太朗、山下倫明、椎名政昭１、緒方一博１、Nigel G. Laing、西野一三、松本直通
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場・福岡サンパレス・福岡国際センター（福岡）
  • Year and Date: 2014-05-21
• [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
  • Filing Date: 2016-12-06