Identification of a novel causative gene for hereditary spastic paraplegia and elucidation of its mechanisms

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16910
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: University of Yamanashi
• Principal Investigator: Koh Kishin 山梨大学, 大学院総合研究部, 医学研究員 (00622557)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 遺伝性痙性対麻痺 / 脊髄小脳変性症 / LYST / GRID2

Outline of Final Research Achievements

In this study, we searched for disease-causing genes to elucidate the pathomechanism of HSP, focusing on how ESCRT-related genes are involved in HSP, but so far we have not identified any new mutations in ESCRT-related genes. On the other hand, we have identified two families with causative genes for other genetic diseases, the first of which is an HSP family with mutations in the LYST gene. We identified four families with LYST mutations and reported on these families after conducting genealogical studies, investigating pathogenetic mechanisms, and reviewing the literature. We have confirmed that three of the reported cases from overseas are included in the family tree. We also identified a family with a mutation of the GRID2 gene and reported it.

Free Research Field

遺伝性痙性対麻痺

Academic Significance and Societal Importance of the Research Achievements

遺伝性痙性対麻痺(HSP)は下肢のつっぱりや筋力低下が主体の遺伝子異常による疾患の総称である。HSPはこれまでに多くの原因遺伝子が同定されており、各遺伝子の機能を解明していくことで神経や筋の働きの解明や治療法の開発につながる。我々はHSP患者の多数の症例からHSPの病態に迫るべく研究を行った。本研究ではLYST遺伝子、GRID2遺伝子の家系を調査しHSPの病態の広がりについて検討した。