Elucidation of the molecular pathogenetic mechanism of West syndrome in the context of Phactr1 gene abnormalities

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08200
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center
• Principal Investigator: Hamada Nanako 愛知県医療療育総合センター発達障害研究所, 分子病態研究部, 主任研究員 (70721835)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ウエスト症候群 / Phactr1

Outline of Final Research Achievements

PHACTR1 is a gene whose mutation was identified in a patient with West syndrome, and its effects on neuronal migration and dendrite formation have been analyzed. In this study, we focused on the clinical significance of PHACTR1 mutations and established patient-derived lymphoblasts for characterization. The results showed no difference in PHACTR1 expression or subcellular localization between normal and patient-derived lymphoblasts, suggesting that differences in binding to actin and protein phosphatase may be the cause of the disease. KCNT1, which binds to PHACTR1, was also suggested to be involved in neuronal migration.

Free Research Field

神経発達

Academic Significance and Societal Importance of the Research Achievements

PHACTR1は日本人ウエスト症候群患者からバリアントが同定された遺伝子である。PHACTR1はシナプス関連分子など主要なてんかん原因分子とは異なり、細胞骨格を構成する分子と相互作用するが、生理作用等は全く不明である。本研究で患者の細胞を用いて得られた結果は、Phactr1の細胞生物学的性状やてんかんの発症機序を理解する一助となり、新規治療法の開発につながる可能性がある。