THE GENETICS OF OPTIC ATROPHY

Autosomal dominant optic atrophy is characterized by visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits and centrocecal scotoma of variable density. Some patients may also develop extraocular characteristics like deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia and ataxia. The clinical expression of this disorder is variable.

Autosomal dominant optic atrophy canbe caused by OPA1 mutations. Another locus for optic atrophy, OPA2, has been mapped to chromosome Xp11.4-p11.21, but no gene has been identified to date. Other loci dientified for optic atrophy (but without a known gene) are: OPA3, OPA4, OPA5, OPA6. Optic atrophy 7 (OPA7) is caused by mutation in the TMEM126A gene.

In addition optic atrophy has been described as part of the clinical spectrum of 3-methylglutaconic aciduria, type I (AUH gene mutation), combined oxidative phosphorylation deficiency 7 (C12orf65 gene mutation), Wolfram syndrome (WFS1 and CISD2 mutations), mitochondrial complex I deficiency (optic neuropathy, NDUFS1 gene mutation), mitochondrial DNA depletion syndrome (POLG mutations), SPG7 (SPG7 gene mutations) and deafness-dystonia-optic atrophy syndrome (TIMM8A gene mutation).