2016 Fiscal Year Final Research Report
Clinical and pathophysiological studies of Alexander disease caused by GFAP gene mutation
| Project/Area Number |
26461297
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | アレキサンダー病 / アストロサイト / GFAP |
|---|
| Outline of Final Research Achievements |
Alexander disease (AxD) is a unique monogenic glial cytopathy caused by mutations in GFAP, which is a specific marker of astrocytes. AxD is divided into three clinical subtype; 1) infantile type, 2) juvenile type, and 3) adult type. We performed the following three studies.
1. GFAP gene test: We tested 28 patients with neurodegenerative disorders for GFAP mutations, but in vain. 2. Identification of a novel disease-causing gene by whole-exome sequencing (WES): We performed WES in two members in a family with autosomal dominant transmission, adult-onset spastic paraplegia with leukodystrophy, and identified 66 candidate genes. 3. Cell biological study: We expressed wildtype and mutant GFAP with a tag-free vector in SW13 cells without intermediate filaments such as GFAP and vimentin, and observed the intracellular distribution of overexpressed GFAP. We found that more aggregations were formed in the mutation which would causes much severe clinical presentation.
|
| Free Research Field |
神経変性疾患の分子遺伝学
|
