2018 Fiscal Year Final Research Report
Elucidation for genetic basis and molecular pathology of infantile epileptic encephalopathy
| Project/Area Number |
16H05160
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human genetics
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
SHIBASAKI kaori
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Keywords | てんかん性脳症 / 新規責任遺伝子 / エクソーム解析 / マウスモデル |
|---|
| Outline of Final Research Achievements |
We identified genetic abnormalities in more than 50% of cases of infantile epileptic encephalopathies by comprehensive gene mutation analysis and copy number variation detection system using whole exome sequencing data. In addition, PPP2R1A, CACNA1G, CSNK2A1, and GABRB2 are identified as novel candidate genes through combining gene mutation data in other large-scale cohorts of brain and nervous diseases and in our study. Furthermore, we identified SLC12A5, CNPY3, CYFIP2 and RHOBTB2 as novel causative genes and reported them together with functional findings in their cell or mouse models. These studies advanced the elucidation of molecular basis of infantile epileptic encephalopathy.
|
| Free Research Field |
分子遺伝学
|
| Academic Significance and Societal Importance of the Research Achievements |
新規原因遺伝子とその機能変化について知見をえることにより、乳児期発症てんかん性脳症の分子病態の理解が進んだ。原因遺伝子変異が多く同定されることは、遺伝子診断できる症例が増えることを意味しており、現時点で約5割の症例で遺伝子診断が可能である。また、2遺伝子に関しては、遺伝子変異をノックインすることによるマウスモデルの確立に成功しており、更なる病態解明と治療薬の開発に繋がる研究成果である。
|
