Identification of a novel causative gene for hereditary spastic paraplegia and elucidation of its mechanisms
| Project/Area Number |
19K16910
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
Koh Kishin 山梨大学, 大学院総合研究部, 医学研究員 (00622557)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 遺伝性痙性対麻痺 / 脊髄小脳変性症 / LYST / GRID2 |
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| Outline of Research at the Start |
遺伝性痙性対麻痺(以下HSP)は厚生労働省の特定疾病に指定されており、現在治療法のない難病の一つである。HSPの治療法の開発には病態解明が不可欠であり、その基礎にある原因遺伝子を同定し、病態機序を解明することが重要である。本研究では細胞内動態のキーとなる膜の動態に関与する遺伝子群に注目し、機能障害による運動神経への影響から新規の治療ターゲットとなる遺伝子変異を抽出する。
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| 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.
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| 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。
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Report
(5 results)
Research Products
(26 results)
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[Journal Article] Chediak-Higashi syndrome presenting as a hereditary spastic paraplegia.2022
Author(s)
Koh K, Tsuchiya M, Ishiura H, Shimazaki H, Nakamura T, Hara H, Suzuyama K, Takahashi M, Tsuji S, Takiyama Y, JASPAC.
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Journal Title
J Hum Genet
Volume: 67
Issue: 2
Pages: 119-121
DOI
Related Report
Peer Reviewed
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[Journal Article] Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia2021
Author(s)
Wiessner M, Suzuki Y, Koh K, Nan H, Ishiura H, Tsuji S, Takiyama Y, Baets J, Synofzik M, Schüle R, Horvath R, Houlden H, Bartesaghi L, Lee HJ, Ampatzis K, Pierson TM, Senderek J.
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Journal Title
Brain
Volume: -
Issue: 5
Pages: 1422-1434
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] UBAP1 mutations cause juvenile-onset hereditary spastic paraplegias (SPG80) and impair UBAP1 targeting to endosomes2019
Author(s)
Nan H, Ichinose Y, Tanaka M, Koh K, Ishiura H, Mitsui J, Mizukami H, Morimoto M, Hamada S, Ohtsuka T, Tsuji S, Takiyama Y
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Journal Title
J Hum Genet
Volume: 64
Issue: 11
Pages: 1055-1065
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] A clinical and genetic study of SPG80, the new type of hereditary spastic paraplegia2020
Author(s)
Ichinose Y, Nan H, Koh K, Tanaka M, Ishiura H, Mitsui J, Mizukami H, Morimoto M, Hamada S, Ohtsuka T, Tsuji S, Takiyama Y
Organizer
The 61th Annual Meeting of the Japanese Society of Neurology
Related Report
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