Exploring rare risk variations of autism spectrum disorders: Whole-exome sequencing of a multiplex family and follow-up study in a Japanese population

• Project/Area Number: 26860917
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: Egawa Jun 新潟大学, 医歯(薬)学総合研究科, 特任准教授 (80648527)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 自閉スペクトラム症 / 全エクソン解析 / 短縮型変異 / 多発罹患家系 / 自閉スぺクトラム症 / 稀なリスク変異 / 複数罹患家系 / 自閉症スペクトラム障害 / 分子遺伝学研究

Outline of Final Research Achievements

To investigate the role of rare heterozygous truncating variations, we performed whole-exome sequencing (WES) in a multiplex ASD family with four affected individuals (two siblings and two maternal cousins), and a follow-up case-control study in a Japanese population.
WES was performed in four individuals (a proband, his affected and unaffected siblings, and their putative carrier mother) from the multiplex ASD family. Rare heterozygous truncating variations prioritized in WES were genotyped in 243 patients and 667 controls. By WES of the multiplex family, we prioritized two rare heterozygous truncating variations, RPS24 Q191X and CD300LF P261fsX266. However, we did not identify these variations in patients or controls in the follow-up study. Our findings suggest that two rare heterozygous truncating variations (RPS24 Q191X and CD300LF P261fsX266) are risk candidates for ASD.

Research Products

• [Journal Article] Novel rare missense variations and risk of autism spectrum disorder: Whole-exome sequencing in two families with affected siblings and a two-stage follow-up study in a Japanese population. (2015)
  • Author(s): Egawa J, Watanabe Y, Wang C, Inoue E, Sugimoto A, Sugiyama T, Igeta H, Nunokawa A, Shibuya M, Kushima I, Orime N, Hayashi T, Okada T, Uno Y, Ozaki N, Someya T
  • Journal Title: PLoS One Volume: 10(3) Issue: 3 Pages: e0119413-e0119413
  • DOI: 10.1371/journal.pone.0119413
  • Peer Reviewed / Open Access
• [Journal Article] Whole-exome sequencing in a family with a monozygotic twin pair concordant for autism spectrum disorder and a follow-up study. (2015)
  • Author(s): 染矢俊幸
  • Journal Title: Psychiatry Res. Volume: 229(1-2) Issue: 1-2 Pages: 599-601
  • DOI: 10.1016/j.psychres.2015.07.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Resequencing and Association Analysis of CLN8 with Autism Spectrum Disorder in a Japanese Population. (2015)
  • Author(s): 染矢俊幸
  • Journal Title: PLoS One. Volume: 10(12) Issue: 12 Pages: e0144624-e0144624
  • DOI: 10.1371/journal.pone.0144624
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rare heterozygous truncating variations and risk of autism spectrum disorder: whole-exome sequencing of a multiplex family and follow-up study in a Japanese population. (2015)
  • Author(s): Inoue E, Watanabe Y, Egawa J, Sugimoto A, Nunokawa A, Shibuya M, Igeta H, Someya T
  • Journal Title: Psychiatry Clin Neurosci Volume: epub Issue: 8 Pages: 472-476
  • DOI: 10.1111/pcn.12274
  • Peer Reviewed
• [Presentation] 自閉スペクトラム症罹患同胞2家系のエクソーム解析および2段階フォローアップ解析 (2015)
  • Author(s): 江川純
  • Organizer: 第45回日本神経精神薬理学会･第37回日本生物学的精神医学会合同年会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-25
• [Presentation] Novel rare missense variations and risk of autism spectrum disorder: whole-exome sequencing in two families with affected siblings and a two-stage follow-up study in a Japanese population. (2015)
  • Author(s): 江川純
  • Organizer: 8th Congress of The Asian Society for Child and Adolescent Psychiatry and Allied Professions 2015.8.19-8.22. Kuala Lumpur
  • Place of Presentation: Kuala Lumpur, Maleysia
  • Year and Date: 2015-08-19
  • Int'l Joint Research