| Project/Area Number |
10670701
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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 |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
MIYABAYASHI S Department of Pediatrics, School of Medicine, Tohoku University, Associate Professor, 大学院・医学系研究科, 助教授 (20174203)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA E Department of Pediatrics, School of Medicine, Tohoku University, Assistant Prof., 医学部・附属病院, 講師 (60233409)
HAGINOYA K Department of Pediatrics, School of Medicine, Tohoku University, Assistant Prof., 医学部・附属病院, 講師 (00208414)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Leigh's disease / mitochondrial DNA / ATPase 6 / pyruvate dehydrogenase deficiency / cytochrome c oxidase deficiency / SURF1 genes / ピルビン酸脱水素欠損症 / ミトコンドリア病 / 変異率 / 低酸素 / 高酸素 / 培養線維芽細胞 |
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| Research Abstract |
We carried out the sequence of E1 subunits that is an activity center of pyruvate dehydrogenase complex (PDHC), and ATP 6 and ATP 8 subunits of ATPase in mitochondrial DNA (mtDNA) by using total DNA from fibroblasts that was obtained from Leigh's disease patients. Furthermore, the presence of the mutation of SURF1 genes was examined in five patients, because it was recognized that cause of disease of cytochrome c oxidase (CCO) deficiency with Leigh's disease lies in this gene in recent years. The mutation of 4 base-insertion and 4 base-deletion were found in exon 11 of the E1 gene from two patients, and 214C>T (Arg>Cys) and 262C>A (Arg>Ser) by exon 2 in another patient with E1 deficiency.
The searching of mtDNA was found 8993T>G mutation in 6 patients and 9176T>C mutation in 2 patients. Also it was found out 8653A>G (Thr>A al) mutation of ATPase 6 subunit to 14 examples. It is found out to 3 examples of sickness models of the others who was doubted mitochondrial disease and this mutation is found out only by one example of normal 100 control examples and disease singularity was estimated that it is getting involved deeply with Leigh's disease, although it is denied. Furthermore we admitted specific deletion including a replication origin of Light chain to the patient of one example.
As a result of sequencing of SURF1 gene two patients showed 779G>T (Gly<Val) mutation in exon 8 and a patient showed the mutations of 881T>A (Leu>Glu) mutation and 915delGC/ins A in exon 9.
In this study, we could reveal about 60% of this disease as novel mutation. A mtDNA gene mutation is 40% and a nuclear gene mutation was 20%. We have expressed that common pathogenesis is an energy metabolic disturbance in a brain, although a cause of Leigh's disease is various. These hypotheses became clear as a mutation is found out even in the searching of the gene that gets involved in an energy metabolism directly.
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