Identification and functional analysis of risk genes in multiplex ADHD families; multidimensional evaluation of neurodevelopmental disorders

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagasaki University
• Principal Investigator: IMAMURA Akira 長崎大学, 病院(医学系), 教授 (40325642)
• Co-Investigator(Kenkyū-buntansha): 吉浦 孝一郎 長崎大学, 原爆後障害医療研究所, 教授 (00304931) ; 黒滝 直弘 香川大学, 医学部, 教授 (20423634) ; 小澤 寛樹 長崎大学, 医歯薬学総合研究科(医学系), 教授 (50260766) ; 金替 伸治 長崎大学, 病院(医学系), 助教 (70404275)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 注意欠如・多動症 / 自閉スペクトラム症 / 神経発達症 / 全エクソンシーケンス / rare-risk variant

Outline of Final Research Achievements

In this study, we performed whole-exome sequencing (WES) on Japanese families, several members of which had ADHD/ASD, and identified variants linked to these disorders. Two families were entered into our study. After written informed consent was obtained from all participants or their parents, clinical symptoms were evaluated using Multi-dimensional Scale for PDD and ADHD. Genomic DNA were extracted from peripheral blood and subsequently subjected to WES. In one of the two families, one SNV was identified in the TRIP12 gene. In the other family, 256 candidate mutations were identified, making it difficult to narrow down the pathogenic variants. Next, we performed TRIP12 mutation screening using samples of sporadic ADHD/ASD patients. We found one patient with a de novo mutation of TRIP12. We will report the clinical information of familial/sporadic cases with TRIP12 mutations.

Free Research Field

児童青年期精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究において、これまで報告されていないTRIP12遺伝子の変異と、その変異を有する患者の臨床情報を得ることができた。このデータは未だ不明である注意欠如・多動症や自閉スペクトラム症等を併存する神経発達症の病態生理解明の一助となる可能性があり、また注意欠如・多動症や自閉スペクトラム症等を併存する神経発達症児に対する早期診断・早期介入や、今後の個別化医療の展開に役立つ可能性がある。