2000 Fiscal Year Final Research Report Summary
GENETIC BACKGROUND OF SPORADIC PARKINSON'S DISEASE
| Project/Area Number |
10670604
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
KOBAYASHI Tomonori Juntendo University, Neurology, Assistant Professor, 医学部, 助手 (50266053)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Yoshikuni Juntendo University, Neurology, Professor, 医学部, 教授 (30049043)
HATTORI Nobutaka Juntendo University, Neurology, Assistant Priofessor, 医学部, 講師 (80218510)
MATSSUMINE Hiroto Juntendo University, Neurology, Assistant Priofessor, 医学部, 助手 (90255670)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Genetic Background / Parkinson's disease / PSP / Parkin / α-Synuclein / Tau / Genotype |
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| Research Abstract |
Four out of the 200 patients had homozygous exonic deletions in the Parkin gene. Their age of onset was consistently yo. We sequenced of all the twelve coding exons and their flanking intronic regions of the Parkin gene on 56 cases with Parkinson's disease. No mutations were detected except for two polymorphisms. We then screened extra cases with PD and control subjects for L272I and V380L polymorphisms. We did not find any apparent difference of the allele frequencies between the PD group and the control group, although polymorphism was too small for the statistical analysis. A real time quantitative PCR method was used for the quantification. We could not detect heterozygous exonic deletion among 52 PD patients. Quantification of Exon 4 of the Parkin Gene on 52 patients and quantification of Exon 3, 4, and 5 on 21 patients did not show heterozygous exonic deletions. We conclude that Parkin gene mutations do contribute to the etiology of certain cases of sporadic PD and majority seems to be caused by yet-to-know factors other than Parkin gene mutations.
The tau gene analyses on pathologically confirmed patients with progressive supranuclear palsy (PSP) showed that all of the six patients were homozygotes of Hl haplotype which was reported to be associated with PSP in Cocasians. However, this kind of haplotype was not polymorphic in Japanese.
We experienced two patients of FTDP-17. They had P301L mutation in exon 10 of the tau gene in common. Aggressivity and disinhibition were the main symptoms in patient 1, whereas parkinsonism was prominent in patient 2. The tau gene genotypes of the two patients were quite contrasting, implying that they did not share common founder for P301L mutation. It also suggested that an unusual phenotype, i.e.parkinsonism of patient 2 might have been associated with either of those rarer genotypes.
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Research Products
(12 results)
