|Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
We studied the ophthalmological and genetic aspects of mitochondrial diseases and myodddddddddddddddddtonic dystrophy, multisystem disorders that affect multiple organs including akeletal muscle, central nervous system, heart, ear and eye. 1. Disease-specific deletion or point mutation of mitochondrial DNA (mtDNA) has been clarified in many clinical entities of mitochondrial diseases, and we confirmed that the ocular manifestations, including chronic progressive external ophthalmoplegia, blephaloptosis, retinochoroidal degeneration and optic atrophy develop in association with either deletion or point mutation of mtDNA.2. Twenty cases out of 40 cases of bilateral optic neorupathy with unknown etiology showed mtDNA/np11778 mutation. Homology analysis of mtDNA sequence encompassing np11778 suggested that the relevant mutation may change the enzyme-substrate binding affinity, and coenzyme Q_<10> treatment gradually recoverd visual function in patients with Lever's hereditary optic neuropathy. 3. Additionally, mutation at np3243 was detected in two patients with diabetes mellitus without neurological symptoms, showing the phenotypic variability of mtDNA abnormalities. 4. Abnormal expansion of CTG-repeat of myotonin protein kinase gene was detected in 11 cases of myotonic dystrophy and showed various ocular manifestations, including cataract, retinochoroidal degeneration and external ophthalmoplegia. Molecular findings of CTG-repeat corresponded with 'anticipation' in one family with typical myotonic dystrophy.