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 Printable version |
Dominant optic atrophy: a mitochondrial pathology |
Neurologie.com. Volume 2, Number 4, 87-91, avril 2010, Revue flash
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 Résumé
Article gratuit
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Author(s) : Patrizia Amati-Bonneau, Christophe Verny, Dan Milea, Pascal Reynier, Dominique Bonneau |
Summary : Autosomal dominant optic atrophy (DOA), also known as Kjer's disease (OMIM 165500) is characterised by moderate to severe loss of visual acuity with insidious onset in early childhood, blue-yellow dyschromatopsia and central scotoma. There is a considerable inter- and intra-familial variation in visual acuity, and the penetrance may be as low as about 40 %. Estimated disease prevalence is between 1:10,000 in Denmark and 1:50,000 worldwide. Histopathological and electrophysiological studies suggest that the underlying defect is retinal ganglion cell degeneration associated with optic atrophy. In 2000 two laboratories reported mutations responsible for the disease in a new gene, OPA1, encoding a mitochondrial targeted dynamin-related GTPase. The gene comprises 31 exons, 30 of which encode a dynamin-related GTPase of 960 amino acids involved in mitochondrial biogenesis. More than 200 OPA1 mutations, mainly family-specific, have been reported so far. À specific genotype-phenotype correlation was observed in patients harboring the R445H OPA1 mutation and optic atrophy associated to deafness. We recently reported the association of optic atrophy and multiple sclerosis-like disorder due to OPA1. Mutations in the OPA1 gene can also be responsible for a syndromic form of DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external ophthalmoplegia and mitochondrial myopathy with Cytochrome C Oxidase (COX) negative and Ragged Red Fibers (RRF). Multiple deletions of mitochondrial DNA (mtDNA) are found in skeletal muscle, thus revealing an unrecognized role of the OPA1 protein in mtDNA stability. Certain OPA1 mutations exert a dominant negative effect responsible for multi-systemic disease, closely related to classical mitochondrial cytopathies, by a mechanism involving mtDNA instability. |
Keywords : dominant optic atrophy, mitochondrial pathology, deafness and optic atrophy |
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