| Project/Area Number |
16590830
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
IZUMI Yuishin The University of Tokushima, Institute of Health Biosciences, Graduate School, Lecturer, 大学院・ヘルスバイオサイエンス研究部, 講師 (10335812)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAJI Ryuji The University of Tokushima, Institute of Health Biosciences, Graduate School, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (00214304)
KAWAKAMI Hideshi Hiroshima University, Research Institute for Radiation Biology and Medicine, Graduate School, Professor, 原爆放射線医科学研究所, 教授 (70253060)
MARUYAMA Hirofumi Hiroshima University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (90304443)
HARADA Masafumi The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (20228654)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | SCA8 / SCA6 / CTG repeat / cerebellar atrophy / 筋強直性ジストロフィー / 若年発症 / 成人発症 |
|---|
| Research Abstract |
We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85≦CTA/CTG≦400) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson's disease (PD), 0.3% in Alzheimer's disease (AD), and 0% in a healthy control group ; the frequency was significantly higher in the SCA group than in the control group. Homozygotes for large alleles were observed only in the SCA group. In 5 SCA patients from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these 5 patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele but no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as CACNA1A through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients. We investigated a family manifesting progressive ataxia, with expanded SCA8 CTA/CTG repeats. Macroscopically, the cerebellum was atrophic, whereas the cereberum and brainstem appeared to be of normal size. Neuropathologically, degeneration of Purkinje, inferior olivary, and nigral neurons and periaqueductal gliosis were evident.
|
