DOMINANT OPTIC ATROPHY DUE TO OPAI MUTATIONS IN THENORTH OF ENGLAND Yu-Wai-Man P, Griffiths PG, Burke A, Sellar PW, Clarke MP, Gnanaraj L, Ah-Kine D, Hudson G, Czermin B, Taylor RW, Horvath R, Chinnery PR The prevalence and natural history of dominant optic atrophy due to OPAI mutations. Ophthalmology 2010;117:1538-1546,1546.e1. Autosomal dominant optic atrophy (DOA) is one of the commonest inherited optic neuropathies. Most of the DOA cases have mutations in the OPAI gene (3q28-q29). Mutations in the OPA3 gene (19q13.2-13.3) can also cause optic atrophy. Although the natural history of DOA is well described, there are no prevalence figures of molecularly confirmed cases in the general population. In this study, the authors performed a population-based epidemiologic and molecular study of presumed DOA in the North of England, which has a relatively stable population. Seventy-six patients with clinical DOA were identified from their Neuro-Ophthalmology and Neurogenetics databases. They underwent OPAI genetic testing using a polymerase chain reaction-based sequencing strategy. If a patient was negative for OPAI mutation, they were screened for large-scale OPA1 rearrangements and OPA3 mutations. Affected family members were identified through contact tracing. They found OPA1 mutations in 57.6% amongst probands with a positive family history of optic atrophy and 14.0% amongst singleton cases. No OPA3 mutations were found. The minimum point prevalence of DOA in the North of England was 2.87 per 100,000 (or 2.09 per 100,000 for OPA1-positive cases), which is comparable to the prevalence of Leber hereditary optic neuropathy in the same area (3.22 per 100,000). The authors then went on to describe the natural history of OPA1+ DOA: the mean age of onset of visual loss was 7.0 years, with a mean rate of visual loss of 0.032 logMar/year (equivalent to 1.5 ETDRS letters/year), but there were large inter- and intrafamilial variability in disease severity.Carmen Chan
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