CLINICAL-FEATURES, MOLECULAR-GENETICS, AND PATHOPHYSIOLOGY OF DOMINANT OPTIC ATROPHY

Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common fo rm of autosomally inherited (non-glaucomatous) optic neuropathy. Patie nts with DOA present with an insidious onset of bilateral visual loss and they characteristically have temporal optic nerve pallor, centroca ecal visual field scotoma, and a colour vision deficit, which is frequ ently blue-yellow. Evidence from histological and electrophysiological studies suggests that the pathology is confined to the retinal gangli on cell. A gene for dominant optic atrophy (OPA1) has been mapped to c hromosome 3q28-qter, and studies are under way to refine the genetic i nterval in which the gene lies, to map the region physically, and henc e to clone the gene. A second locus for dominant optic atrophy has rec ently been shown to map to chromosome 18q12.2-12.3 near the Kidd blood group locus. The cloning of genes for dominant optic atrophy will pro vide important insights into the pathophysiology of the retinal gangli on cell in health and disease. These insights may prove to be of great value in the understanding of other primary ganglion cell diseases, s uch as the mitochondrially inherited Leber's hereditary optic neuropat hy and other diseases associated with ganglion cell loss, such as glau coma.