Exploring gene for a Japanese family of an autosomal dominant nemaline myopathy associated with dilated cardiomyopathy

• Project/Area Number: 23591233
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: ICHIKAWA Yaeko 東京大学, 医学部附属病院, 助教 (90341081)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ネマリンミオパチー / 拡張型心筋症 / 網羅的ゲノム解析 / 次世代シークエンサー / ゲノム解析研究 / 原因遺伝子 / ミオパチー

Research Abstract

This study is about molecular genetics of a Japanese family of an autosomal dominant nemaline myopathy associated with dilated cardiomyopathy. Multipoint parametric linkage analysis revealed the target region spanning approximately 800Mb. Massively parallel sequencing for the proband was accomplished. Subsequently, the novel nonsynonymous variants were subjected to direct nucleotide sequence analysis for confirmation, and screened by Japanese genetic variation database (Human Genetic Variation Database) and in-house database of normal and disease control. The two of those variants were remaining as candidate pathogenic mutations. We are studying about which variant is the causative mutation of this family by functional analysis.

Research Products

• [Journal Article] Rapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing (2014)
  • Author(s): Doi K, Monjo T, Hoang PH, Yoshimura J, Yurino H, Mitsui J, Ishiura H, Takahashi Y, Ichikawa Y, Goto J, Tsuji S, Morishita S
  • Journal Title: Bioinformatics Volume: 30 Pages: 815-22
• [Journal Article] An open trial of long-term testosterone suppression in spinal and bulbar muscular atrophy (2013)
  • Author(s): Yamamoto T, Yokota K, Amao R, Maeno T, Haga N, Taguri M, Ohtsu H, Ichikawa Y, Goto J, Tsuji S
  • Journal Title: Muscle Nerve Volume: 47 Pages: 816-22
• [Journal Article] Mutations in COQ2 in familial and sporadic multiple-system atrophy (2013)
  • Author(s): Multiple-System Atrophy Research Collaboration
  • Journal Title: N Engl J Med Volume: 369 Pages: 233-44
• [Journal Article] Exome analysis reveals a Japanese family with spinocerebellar ataxia, autosomal recessive 1 (2013)
  • Author(s): Ichikawa Y, Ishiura H, Mitsui J, Takahashi Y, Kobayashi S, Takuma H, Kanazawa I, Doi K, Yoshimura J, Morishita S, Goto J, Tsuji S
  • Journal Title: J Neurol Sci Volume: 331 Pages: 158-60
• [Journal Article] ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19 (2013)
  • Author(s): Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, Kimura F, Murayama S, Onodera O, Nishizawa M, Yoshida M, Atsuta N, Sobue G; JaCALS, Fifita JA, Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez P, Brown RH Jr, Nomoto M, Elenius K, Rouleau GA, Fujiyama A, Morishita S, Goto J, Tsuji S
  • Journal Title: Am J Hum Genet Volume: 93 Pages: 900-5
• [Journal Article] Culture-negative brain abscess with Streptococcus intermedius infection with diagnosis established by direct nucleotide sequence analysis of the 16s ribosomal RNA gene (2012)
  • Author(s): Saito N, Hida A, Koide Y, Ooka T, Ichikawa Y, Shimizu J, Mukasa A, Nakatomi H, Hatakeyama S, Hayashi T, Tsuji S
  • Journal Title: Intern Med Volume: 51 Pages: 211-6
  • NAID: 130002062067
• [Journal Article] Increased gene dosage of myelin protein zero causes Charcot-Marie- Tooth disease (2012)
  • Author(s): Maeda MH, Mitsui J, Soong BW, Takahashi Y, Ishiura H, Hayashi S, Shirota Y, Ichikawa Y, Matsumoto H, Arai M, Okamoto T, Miyama S, Shimizu J, Inazawa J, Goto J, Tsuji S
  • Journal Title: Ann Neurol Volume: 71 Pages: 84-92
• [Journal Article] C9ORF72 Repeat Expansion in Amyotrophic Lateral Sclerosis in the Kii Peninsula of Japan (2012)
  • Author(s): Ishiura H, Takahashi Y, Mitsui J, Yoshida S, Kihira T, Kokubo Y, Kuzuhara S, Ranum LP, Tamaoki T, Ichikawa Y, Date H, Goto J, Tsuji S
  • Journal Title: Arch Neurol Volume: 69 Pages: 1154-8
• [Journal Article] The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement (2012)
  • Author(s): Ishiura H, Sako W, Yoshida M, Kawarai T, Tanabe O, Goto J, Takahashi Y, Date H, Mitsui J, Ahsan B, Ichikawa Y, Iwata A, Yoshino H, Izumi Y, Fujita K, Maeda K, Goto S, Koizumi H, Morigaki R, Ikemura M, Yamauchi N, Murayama S, Nicholson GA, Ito H, Sobue G, Nakagawa M, Kaji R, Tsuji S
  • Journal Title: Am J Hum Genet Volume: 91 Pages: 320-9
• [Journal Article] Mutations in KCND3 cause spinocerebellar ataxia type 22 (2012)
  • Author(s): Lee YC, Durr A, Majczenko K, Huang YH, Liu YC, Lien CC, Tsai PC, Ichikawa Y, Goto J, Monin ML, Li JZ, Chung MY, Mundwiller E, Shakkottai V, Liu TT, Tesson C, Lu YC, Brice A, Tsuji S, Burmeister M, Stevanin G, Soong BW
  • Journal Title: Ann Neurol Volume: 72 Pages: 859-69
• [Journal Article] C9ORF72 repeat expansion in amyotrophic lateral sclerosis in the Kii peninsula of Japan. (2012)
  • Author(s): Ishiura H, Kokubo Y.
  • Journal Title: Arch Neurol. Volume: 69(9) Issue: 9 Pages: 1154-1158
  • DOI: 10.1001/archneurol.2012.1219
  • Peer Reviewed
• [Journal Article] The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement. (2012)
  • Author(s): Ishiura H
  • Journal Title: Am J Hum Genet. Volume: 91(2) Issue: 2 Pages: 320-9
  • DOI: 10.1016/j.ajhg.2012.07.014
  • Peer Reviewed
• [Journal Article] Mutations in KCND3 cause spinocerebellar ataxia type 22. (2012)
  • Author(s): Lee YC, Durr A, Majczenko K, Huang YH, Liu YC, Lien CC, Tsai PC, Ichikawa Y et al., ,
  • Journal Title: Ann Neurol. Volume: 72 Issue: 6 Pages: 859-69
  • DOI: 10.1002/ana.23701
  • Peer Reviewed
• [Journal Article] 多系統萎縮症 臨床試験に向けての現況と課題 (2012)
  • Author(s): 市川弥生子
  • Journal Title: BRAIN and NERVE Volume: 64 Pages: 1141-1149
  • NAID: 40019456431
• [Journal Article] Culture-negative Brain Abscess with <i>Streptococcus intermedius</i> Infection with Diagnosis Established by Direct Nucleotide Sequence Analysis of the 16S Ribosomal RNA Gene (2012)
  • Author(s): N.Saito, et al
  • Journal Title: Internal Medicine Volume: 51 Issue: 2 Pages: 211-216
  • DOI: 10.2169/internalmedicine.51.6419
  • NAID: 130002062067
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Increased gene dosage of myelin protein zero causes Charcot-Marie-Tooth disease (2012)
  • Author(s): Maeda MH, Ishiura H, et al
  • Journal Title: Ann Neurol Volume: 71 Issue: 1 Pages: 84-92
  • DOI: 10.1002/ana.22658
  • Peer Reviewed
• [Journal Article] Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1 (2011)
  • Author(s): Ishiura H, Fukuda Y, Mitsui J, Nakahara Y, Ahsan B, Takahashi Y, Ichikawa Y, Goto J, Sakai T, Tsuji S
  • Journal Title: Neurogenetics Volume: 12 Pages: 117-21
• [Journal Article] A Japanese family of a novel autosomal dominant nemaline myopathy associated with dilated cardiomyopathy. (2011)
  • Author(s): Ichikawa Y, Ishiura H, Goto J, Kowa H, Oya Y, Date H, Tsuji S
  • Journal Title: Neurology Volume: 76 (Suppl 4)
  • Peer Reviewed
• [Journal Article] Therapeutic trial design issues for future disease-modifying therapy of multiple system atrophy (2011)
  • Author(s): Ichikawa Y, Goto J, Nakahara Y, Mitsui J, Tsuji S
  • Journal Title: Rinsho Shinkeigaku Volume: 51 Pages: 910-913
  • NAID: 130004504910
• [Presentation] 神経・筋疾患における遺伝子検査の有用性 (2013)
  • Author(s): 市川弥生子,石浦浩之,三井純,松川敬志,田中真生,高橋祐二,後藤順,辻省次
  • Organizer: 第20回日本遺伝子診療学会大会
  • Place of Presentation: 浜松
  • Year and Date: 2013-07-20
• [Presentation] 神経内科領域における遺伝子診断の現況と課題 (2013)
  • Author(s): 市川弥生子,西垣昌和,今井靖,平田恭信,辻省次,後藤順
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2013-05-24
• [Presentation] 神経内科領域における遺伝子診断の現況と課題. (2013)
  • Author(s): 市川弥生子, 西垣昌和, 今井 靖, 平田恭信, 辻 省次, 後藤 順
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] 神経内科・循環器内科領域における遺伝子診断の状況 (2012)
  • Author(s): 市川弥生子,西垣昌和,今井靖,平田恭信,辻省次,後藤順
  • Organizer: 第57回日本人類遺伝学会大
  • Place of Presentation: 東京
  • Year and Date: 2012-10-25
• [Presentation] A four-generation Japanese family with autosomal dominant nemaline myopathy associated with dilated cardiomyopathy (2012)
  • Author(s): Y. Ichikawa, J. Goto, H. Ishiura, Y. Oya, H. Kowa, J. Shimizu, H. Date, S. Tsuji
  • Organizer: 17^<th> International congress of the world muscle society
  • Place of Presentation: Perth, Australia
  • Year and Date: 2012-10-11
• [Presentation] 多系統萎縮症の早期症例における診断基準の検討 (2012)
  • Author(s): 市川弥生子,中原康雄,百瀬義雄,後藤順,辻省次
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-24
• [Presentation] A four-generation Japanese family with autosomal dominant nemaline myopathy associated with dilated cardiomyopathy (2012)
  • Author(s): Y. Ichikawa, J. Goto, H. Ishiura, Y. Oya, H. Kowa, J. Shimizu, H. Date, S. Tsuji
  • Organizer: 17th International congress of the world muscle society
  • Place of Presentation: Perth, Australia
• [Presentation] 多系統萎縮症の早期症例における診断基準の検討 (2012)
  • Author(s): 市川 弥生子, 中原 康雄, 百瀬 義雄, 後藤 順, 辻 省次
  • Organizer: 第53回 日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] 神経内科・循環器内科領域における遺伝子診断の状況 (2012)
  • Author(s): 市川弥生子、西垣昌和、今井 靖、平田恭信、辻 省次、後藤 順
  • Organizer: 第57回 日本人類遺伝学会大会
  • Place of Presentation: 東京
• [Presentation] Assessment of clinical usefulness of genetic diagnosis in neurology department of hospital (2011)
  • Author(s): Y. Ichikawa, H. Ishiura, J. Mitsui, T. Matsukawa, Y. Takahashi, H. Naruse, M. Taira, S. Tsuji, J. Goto
  • Organizer: 12^<th> International Conference of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2011-10-13
• [Presentation] 神経内科領域における前方向的コホート研究から見えてきたもの. MSAに対するdisease-modifying therapy実現のための臨床治験デザイン (2011)
  • Author(s): 市川弥生子,後藤順,中原康雄,三井純,辻省次
  • Organizer: 第52回日本神経学会学術大会シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-19
• [Presentation] 多系統萎縮症の運動機能における経時的推移 (2011)
  • Author(s): 市川弥生子,百瀬義雄,中原康雄,後藤順,辻省次, JAMSAC (Japan MSA research consortium)
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] A Japanese family of a novel autosomal dominant nemaline myopathy associated with dilated cardiomyopathy (2011)
  • Author(s): Ichikawa Y, Ishiura H, Goto J, Kowa H, Oya Y, Date H, Tsuji S
  • Organizer: American Academy of Neurology 63^<rd> Annual Meeting
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2011-04-13
• [Presentation] A Japanese family of a novel autosomal dominant nemaline myopathy associated with dilated cardiomyopathy (2011)
  • Author(s): Ichikawa Y, Ishiura H, Goto J, Kowa H, Oya Y, Date H, Tsuji S
  • Organizer: American Academy of Neurology 63rd Annual Meeting
  • Place of Presentation: Honolulu, USA
• [Presentation] Assessment of clinical usefulness of genetic diagnosis in neurology department of hospital (2011)
  • Author(s): Y. Ichikawa, H. Ishiura, J. Mitsui, T. Matsukawa, Y. Takahashi, H. Naruse, M. Taira, S. Tsuji, J. Goto
  • Organizer: 12th International Conference of Human Genetics
  • Place of Presentation: Montreal, Canada
• [Presentation] 多系統萎縮症の運動機能における経時的推移 (2011)
  • Author(s): JAMSAC, 市川弥生子、百瀬義雄、中原康雄、後藤 順、辻 省次
  • Organizer: 第52回日本神経学会
  • Place of Presentation: 名古屋
• [Presentation] MSAに対するdisease-modifying therapy 実現のための臨床治験デザイン (2011)
  • Author(s): 市川弥生子 、後藤 順、中原康雄、三井 純、辻 省次
  • Organizer: 第52回日本神経学会 シンポジウム
  • Place of Presentation: 名古屋
• [Presentation] 神経・筋疾患における遺伝子検査の有用性
  • Author(s): 市川弥生子, 石浦浩之, 三井 純, 松川敬志, 田中真生, 高橋祐二, 後藤 順, 辻 省次
  • Organizer: 第20回日本遺伝子診療学会大会
  • Place of Presentation: 東京(アクトシティ浜松コングレスセンター)
• [Book] アクチュアル脳・神経疾患の臨床小脳と運動失調「JAMSAC研究」 (2013)
  • Author(s): 市川弥生子
  • Publisher: 中山書店
• [Book] アクチュアル 脳・神経疾患の臨床 小脳と運動失調 (2013)
  • Author(s): 市川弥生子 （総編集：辻 省次）
  • Total Pages: 336
  • Publisher: 中山書店
• [Book] Annual Review神経2012各種疾患変性疾患「MSA update」 (2012)
  • Author(s): 市川弥生子
  • Publisher: 中外医学社
• [Book] カラー版内科学「脊髄小脳変性症」 (2012)
  • Author(s): 市川弥生子
• [Book] カラー版 内科学 (2012)
  • Author(s): 市川弥生子 (総編集：門脇 孝、永井良三)
  • Total Pages: 1929
  • Publisher: 西村書店
• [Book] Annual Review 神経 2012 「MSA update」 (2012)
  • Author(s): 市川弥生子
  • Publisher: 中外医学社