A genetic study of patients with multiple system atrophy from consanguineous families

• Project/Area Number: 25860700
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: MITSUI Jun 東京大学, 医学部附属病院, 助教 (70579862)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 遺伝学 / 連鎖解析 / 次世代シーケンサー / 神経変性疾患 / エクソーム解析 / 常染色体劣性遺伝性 / 分子遺伝学的研究

Outline of Final Research Achievements

Two consanguineous families with multiple system atrophy were newly identified, and in total, six pedigrees with multiple system atrophy were subjected to this study. In the parametric linkage analysis allowing for heterogeneity, we did not find any apparent candidate loci. Subsequently, exome sequencing analysis was conducted in six probands with multiple system atrophy. Removing variants with a minor allele frequency > 0.1%, several candidate variants in the homozygous state remained in each pedigree. However, we did not detect any common variants shared in more than one family.

Research Products

• [Journal Article] Variants associated with Gaucher disease in multiple system atrophy (2015)
  • Author(s): Mitsui J, Matsukawa T, Sasaki H, Yabe I, Nakahara Y, Momose Y, Takahashi Y, Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Nishizawa M, Watanabe H, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, Tsuji S, et al.
  • Journal Title: Ann Clin Transl Neurol. Volume: 2 Issue: 4 Pages: 417
  • DOI: 10.1002/acn3.185
  • URL: https://localhost/en/publications/c946bad2-a238-4d0e-a396-6d33b3922ab7
  • Peer Reviewed / Open Access
• [Journal Article] The first Japanese familial case of spinocerebellar ataxia 23 with a novel mutation in the PDYN gene (2015)
  • Author(s): 1.Saigoh K, Mitsui J, Hirano, M, Sioyama M, Samukawa M, Ichikawa Y, Goto J, Tsuji S, Kusunoki S
  • Journal Title: Parkinsonism Relat Disord Volume: 21 Issue: 3 Pages: 332-334
  • DOI: 10.1016/j.parkreldis.2014.12.028
  • Peer Reviewed
• [Journal Article] Genomic Aspects of Sporadic Neurodegenerative Diseases. (2014)
  • Author(s): Mitsui J and Tsuji S.
  • Journal Title: Biochem Biophys Res Commun Volume: 452 Issue: 2 Pages: 221-225
  • DOI: 10.1016/j.bbrc.2014.07.098
  • Peer Reviewed / Open Access
• [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 Issue: 6 Pages: 815-822
  • DOI: 10.1093/bioinformatics/btt647
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan. (2014)
  • Author(s): Yamada, M., M. Tanaka, M. Takagi, S. Kobayashi, Y. Taguchi, S. Takashima, K. Tanaka, T. Touge, H. Hatsuta, S. Murayama, Y. Hayashi, M. Kaneko, H. Ishiura, J. Mitsui, N. Atsuta, G. Sobue, N. Shimozawa, T. Inuzuka, S. Tsuji and I. Hozumi
  • Journal Title: Neurology Volume: 82 Issue: 8 Pages: 705-712
  • DOI: 10.1212/wnl.0000000000000143
  • Peer Reviewed
• [Journal Article] Mutations in COQ2 in familial and sporadic multiple-system atrophy the multiple-system atrophy research collaboration (2013)
  • Author(s): Mitsui J, et. al.
  • Journal Title: N Engl J Med Volume: 369 Issue: 3 Pages: 233
  • DOI: 10.1056/nejmoa1212115
  • URL: https://localhost/en/publications/228d3923-3adb-4e39-bd77-14bb10709e09
  • Peer Reviewed
• [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 Issue: 1-2 Pages: 158
  • DOI: 10.1016/j.jns.2013.05.018
  • URL: https://localhost/en/publications/7c6fc9c0-40f8-4eb1-96ca-f220c74f7fb7
  • Peer Reviewed
• [Journal Article] Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients. (2013)
  • Author(s): Ishii A, Saito Y, Mitsui J, Ishiura H, Yoshimura J, Arai H, Yamashita S, Kimura S, Oguni H, Morishita S, Tsuji S, Sasaki M, Hirose S.
  • Journal Title: PLoS One Volume: 8 Issue: 2 Pages: e56120-e56120
  • DOI: 10.1371/journal.pone.0056120
  • Peer Reviewed
• [Journal Article] A recurrent de novo FAM111A mutation causes Kenny–Caffey syndrome type 2. (2013)
  • Author(s): Isojima T, Doi K, Mitsui J, Oda Y, Tokuhiro E, Yasoda A, Yorifuji T, Horikawa R, Yoshimura J, Ishiura H, Morishita S, Tsuji S, and Kitanaka S.
  • Journal Title: J Bone Mineral Res Volume: 29 Issue: 4 Pages: 992-998
  • DOI: 10.1002/jbmr.2091
  • Peer Reviewed / Open Access
• [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, (33名省略）, Morishita S, Goto J and Tsuji S.
  • Journal Title: Am J Hum Genet Volume: 93 Issue: 5 Pages: 900-905
  • DOI: 10.1016/j.ajhg.2013.09.008
  • Peer Reviewed
• [Presentation] 多系統萎縮症の疾患関連遺伝子の探索 (2014)
  • Author(s): 三井 純，松川 敬志，石浦 浩之，市川 弥生子，後藤 順，JAMSAC，村山 繁雄，高嶋 博，佐々木 秀直，辻 省次．
  • Organizer: 第55回神経学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-23
• [Presentation] Genetics in Multiple System Atrophy. (2014)
  • Author(s): Mitsui J
  • Organizer: The 13th International Parkinson’s disease Symposium in Takamatsu.
  • Place of Presentation: Takamatsu, Japan
  • Invited
• [Presentation] Mutations in COQ2 in Familial and Sporadic Multiple-system Atrophy. (2014)
  • Author(s): Mitsui J
  • Organizer: 3rd GCOE Workshop between BGI and UT.
  • Place of Presentation: Tokyo, Japan
  • Invited
• [Presentation] Molecular genetics of multiple system atrophy: results from the Japan Multiple System Atrophy Research Consortium. (2013)
  • Author(s): JAMSAC (Japan Multiple System Atrophy Research Consortium), Jun Mitsui, Yaeko Ichikawa, Jun Goto, Shoji Tsuji.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorder
  • Place of Presentation: Sydney, Australia
• [Presentation] Mutations of COQ2 in Familial and Sporadic Multiple System Atrophy. (2013)
  • Author(s): Mitsui J, Matsukawa T, Ishiura H, et al.
  • Organizer: American Society of Human Genetics 63rd Annual Meeting
  • Place of Presentation: Boston, US
• [Presentation] エクソーム解析による遺伝的異質性の高い疾患に対する遺伝子検査． (2013)
  • Author(s): 三井 純，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
• [Presentation] COQ2変異は家族性・孤発性多系統萎縮症と関連する． (2013)
  • Author(s): 三井 純，松川 敬志，石浦 浩之，福田 陽子，市川 弥生子，伊達 英俊，Budrul Ahsan，中原 康雄，百瀬 義雄，高橋 祐二，岩田 淳，後藤 順，The MSA Research Collaboration，辻 省次．
  • Organizer: 第58回日本人類遺伝学会
  • Place of Presentation: 仙台