| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Research Abstract |
1) Resequence analysis of whole mitochondrial DNA
The investigator analyzed whole mitochondrial DNA sequence of more than 250 patients with mitochondrial diseases. We found 14674 mutation within the glutamate tRNA in the patients with benign COX deficiency, two adjacent mutations of 3243 within leucine tRNA, 9155 mutation within tyrosine tRNA in the patient with severe renal involvement, 14559 mutation in the patient with optic atrophy and dystonia. Many candidate mutations for disease were also found (617, 8296, 12129, 14729 mutations in tRNA genes and 3481, 5698, 6890, 7444, 8114, 9035, 9801 mutations in protein-coding regions).
2) Molecular biological and biochemical analyses using culture cells from the patients
Cybrids made by fusion of patient-derived cell cytoplasts with rho-zero cells were analyzed biochemically. 14674, 3244 and 9155 mutations were proved to be causes for diseases.
3) Point mutations in the leucine tRNA region and anticodon modification defect
Point mutations such as 3243 and 3271 mutation present in MELAS patients had anticodon modification defect, but other mutation present in non-MELAS patients did not show the defect. It suggests that this modification defect had some relationship with MELAS phenotype.
4) Germanium-induced marmoset model of mitochondrial disease
Marmosets supplemented with 0.5% germanium exhibited deafness clinically. Pathological evidence for mitochondrial abnormalities was confirmed in the tissue of Corti apparatus in the internal ear.
5) Clinical summary of 136 patients with single deletion of mitochondrial DNA
We summarized kinds and frequency of the deletion, clinical phenotype, onset ages and so on in the 136 patients with single deletions of mitochondrial DNA. The study revealed that the length of the deletion, COX subunit involvement in the deleted region, and early onset were risk factors for Kearn-Sayre syndrome.
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