The Italian reappraisal of the most frequent genetic defects in hereditary optic neuropathies and the global top 10.

We read with great interest the recent publication by Rocatcher and colleagues[1] entitled 'The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands', reporting on the experience of a national diagnostic centre for hereditary optic neuropathies (HON) in France. This flexible approach enlarges the number of genes screened, compared with the fixed number of 87 genes included in the custom targeted gene panel reported by Rocatcher I et al i .[1] Therefore, we found pathogenic variants in 30 genes, of which 18 were in single families (8.4%), whereas in the French cohort, only 21 genes were found to carry pathogenic variants, with seven singleton cases (1.5%). This is currently the standard algorithm followed by I in silico i panel analysis, prioritizing variants in known HON genes, to eventually discover new disease genes. Thus, the top 10 genes are consolidated by the contribution of the Italian cohort, with I OPA1 i , I WFS1 i and I ACO2 i accounting for 76% of diagnosed HON, due to a nuclear gene defect. [Extracted from the article]