Synaptic dysfunction of Autism spectrum disorder relating to the dysfunction of scaffold protein and circadian related genes.

• Project/Area Number: 26893252
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Jichi Medical University
• Principal Investigator: Matsumoto Ayumi 自治医科大学, 医学部, 助教 (20458318)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 自閉症スペクトラム / 発達障害 / サーカディアンリズム異常 / サーカディアンリズム障害 / 自閉症 / シナプス

Outline of Final Research Achievements

Array comparative genomic hybridization (CGH) analysis for an autism spectrum disorder (ASD) patient, a 73 Kb duplication at 19q13.33　including LIN7B was detected. We then identified a novel frameshift mutation in LIN7B in an ASD patient.
In utero electroporation, suppression of Lin-7B in utero electroporation method resulted the migration of cortical neurons and axon extension to the contralateral hemisphere was delayed.
Lin-7B is possible to be implicated in the pathophysiology in ASD, and abnormal neuronal migration and interhemispheric axon development might contribute to the clinical symptoms of ASD. About 44-83% of children with ASD are suffering from sleep problems. We screened circadian-relevant genes in ASD with and without sleep disturbance group, and control group. In all of ASD (P=0.001), non-synonymous mutations were significantly frequently detected than control group. Circadian-relevant genes may be involved in the psychopathology of ASD.

Research Products

• [Journal Article] Morphological characterization of Class III phosphoinositide 3-kinase during mouse brain development. (2016)
  • Author(s): Inaguma Y, Ito H, Iwamoto I, Matsumoto A, Yamagata T, Tabata H, Nagata K-I
  • Journal Title: Med Mol Morphol Volume: 49 Issue: 1 Pages: 28-33
  • DOI: 10.1007/s00795-015-0116-1
  • Peer Reviewed / Open Access
• [Journal Article] Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients. (2015)
  • Author(s): Yang Z, Matsumoto A, Nakayama K, Jimbo EF, Kojima K, Nagata KI, et al.
  • Journal Title: Brain Dev. Volume: 15 Issue: 1 Pages: 91-9
  • DOI: 10.1016/j.braindev.2015.04.006
  • Peer Reviewed / Open Access
• [Journal Article] 6q21-22 deletion syndrome with interrupted aortic arch. (2015)
  • Author(s): Matsumoto A, Nozaki Y, Minami T, Jimbo EF, Shiraishi H, Yamagata T. Human genom variation.
  • Journal Title: Human genom variation. Volume: 2 Issue: 1 Pages: 15015-15015
  • DOI: 10.1038/hgv.2015.15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders. (2015)
  • Author(s): Mizuno M, Matsumoto A, Hamada N, Ito H, Miyauchi A, Jimbo EF, Momoi MY, Tabata H, Yamagata T, Nagata K.
  • Journal Title: J Neurochem Volume: 132 Issue: 1 Pages: 61-69
  • DOI: 10.1111/jnc.12943
  • Peer Reviewed / Open Access
• [Presentation] Genetic analysis for circadian rhythm abnormality in autism spectrum disorder (2015)
  • Author(s): Ayumi Matsumoto, Yutaka Inaguma, Zhiliang Yang,Yuko Nakano, Masahide Goto, Kazuhiro Nakayama, Eriko F. Jimbo, Hitoshi Osaka, Sadahiko Iwamoto, Koichi Nagata, Takanori Yamagata
  • Organizer: American society of human genetics 65th annual meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] TIMELESS mutation in a patient with autism spectrum disorder (ASD) and circadian rhythm disorder. (2015)
  • Author(s): 松本 歩、楊 志亮、中野 裕子、中山 一大、神保 恵理子、岩本 禎彦、永田浩一、山形 崇倫
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-27 – 2015-05-30
• [Presentation] TIMELESS mutation in a patient with autism spectrum disorder (ASD) and circadian rhythm disorder. (2015)
  • Author(s): 松本 歩、楊 志亮、中野 裕子、中山 一大、神保 恵理子、岩本 禎彦、永田浩一、山形 崇倫
  • Organizer: 小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-27