2019 Fiscal Year Final Research Report
Elucidation of pathomechanism common to inclusion body myopathies and search for therapeutic target molecules
| Project/Area Number |
17K16107
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
Izumi Rumiko 東北大学, 大学病院, 医員 (60571453)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Keywords | ミオパチー / 筋炎 / 封入体 / 縁取り空胞 / 蛋白分解系 |
|---|
| Outline of Final Research Achievements |
We performed genetic analysis using a next-generation sequencer for a total of 25 cases of hereditary inclusion body myopathy (hIBM) and sporadic inclusion body myositis (sIBM) for the extraction of genomic variants related to the pathogenesis of inclusion body formation and skeletal muscle degeneration.In addition, whole-genome long-read sequencing was performed on 3 cases of hIBM to detect pathogenic repeat sequence structure. From these analyses, we identified 24 rare and 27 novel variants, besides known mutations in 3 hIBM cases. From transcriptome analysis of skeletal muscle tissue RNA, 39 genes that were significantly different in expression level were extracted in comparison between the hIBM group and the control group.
|
| Free Research Field |
脳神経内科
|
| Academic Significance and Societal Importance of the Research Achievements |
治療法は未確立であり進行性の筋萎縮・筋力低下のため著しい機能障害を起こす遺伝性封入体ミオパチー（hIBM）と孤発性封入体筋炎（sIBM）の遺伝子解析を行い、51の新規あるいはレアバリアントを検出した。今後のこれらのデータと新規症例のデータ照合、生検筋を用いた検討の継続により、封入体形成に関係する新規病因遺伝子を明らかとできる可能性がある。またトランスクリプトーム解析では39遺伝子にて発現有意差を認めており、この中に治療法開発の可能性標的分子が含まれている可能性がある。今後治療法確立へ向けて解析を継続する。
|
