Molecular genetic basis of primary inherited optic neuropathies.
OBJECTIVE
To review the molecular genetic basis of primary inherited optic neuropathies.


METHODS
Medline and Embase search.


RESULTS
Inherited optic neuropathies are a genetically diverse group of disorders that present with reduced visual acuity and the clinical appearance of optic atrophy. The inherited optic neuropathies may be sporadic or familial, in which case the mode of inheritance may be Mendelian (autosomal dominant, autosomal recessive, X-linked recessive) or non-Mendelian (mitochondrial). Two genes for dominantly inherited optic atrophy have been mapped (OPA1 and OPA4), of which the gene has been identified in one (OPA1). A gene for recessive optic atrophy (OPA3) has also been identified. X-linked optic atrophy (OPA2) has been mapped but to date no gene has been identified. Mutations in mitochondrial DNA have been identified in Leber's hereditary optic neuropathy.


CONCLUSIONS
Mutations in genes from both the nuclear and mitochondrial genomes appear to be responsible. Mitochondrial dysfunction, in the broadest sense, is emerging as central to the pathogenesis of this group of conditions.
Votruba
M
M
School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK. votrubam@cardiff.ac.uk
D020558:GTP Phosphohydrolases / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D005901:Glaucoma / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D015418:Optic Atrophies, Hereditary / Q000235:genetics*; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D012165:Retinal Ganglion Cells / Q000502:physiology
D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human