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J. Rozet, F. Barbet, J.–L.L. Dufier, A. Munnich, J. Kaplan; A Third Locus for Dominant Optic Atrophy on Chromosome 22q . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2292.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Autosomal dominant optic atrophies (ADOA) are by far the most common mendelian cause of primary hereditary optic neuropathies. A major locus has been mapped to chromosome 3q28–q29 and the OPA1 gene identified. A second locus, OPA4, has been mapped on chromosome 18q12.2–q12.3 in a family whose phenotype was similar to that of OPA1 patients. The purpose of this study was to map new OPA loci in two families of our series excluding both OPA1 and OPA4 loci. Methods: Two unrelated families of French origin affected with an autosomal dominant optic atrophy were ascertained through the Genetic consultation. The phenotype of affected patients of both families was similar to that of patients harbouring OPA1 mutations. Linkage to the OPA1 and OPA4 loci was excluded in both families using markers flanking each of these two ADOA loci prior to a 10 cM genome–wide search for the disease–causing gene using fluorescent oligonucleotides flanking the 382 polymorphic markers of the Genescan Linkage Mapping Set, Version II (Applied Biosystems). Results: All affected patients of each family were found to share a common haplotype on chromosome 22q12.1–q13.1. Obligatory recombination events allowed to defined a 10.4 cM genetic interval between the D22S1148 and D22S283 loci. A maximum lod score of Zmax = 3,75 at Θ = 0 was obtained with the marker AFMa043tf9 at the D22S1176 locus. For this calculation, the penetrance was set at 100% (12/12 individuals with a disease haplotype were affected with ADOA). Conclusions:We report the mapping of a third locus of ADOA, OPA5, on chromosome 22q12.1–q13.1. It is worth noting that the phenotype of all patients linked to OPA5 is similar to that of patients linked to OPA1.To date, 73 known genes and as many predicted genes are contained in the OPA5 interval. The screening of these genes is ongoing.
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