Abstract：
Hereditary optic neuropathies are caused by the degeneration of retinal ganglion cells whose axons form the optic nerves, with a consistent genetic heterogeneity. As part of our diagnostic activity, we retrospectively evaluated the combination of Leber hereditary optic neuropathy mutations testing with the exon sequencing of 87 nuclear genes on 2186 patients referred for suspected hereditary optic neuropathies. The positive diagnosis rate in individuals referred for Leber hereditary optic neuropathy testing was 18% (199/1126 index cases), with 92% (184/199) carrying one of the three main pathogenic variants of mitochondrial DNA (m.11778G>A, 66.5%; m.3460G>A, 15% and m.14484T>C, 11%). The positive diagnosis rate in individuals referred for autosomal dominant or recessive optic neuropathies was 27% (451/1680 index cases), with 10 genes accounting together for 96% of this cohort. This represents an overall positive diagnostic rate of 30%. The identified top 10 nuclear genes included OPA1, WFS1, ACO2, SPG7, MFN2, AFG3L2, RTN4IP1, TMEM126A, NR2F1 and FDXR. Eleven additional genes, each accounting for less than 1% of cases, were identified in 17 individuals. Our results show that 10 major genes account for more than 96% of the cases diagnosed with our nuclear gene panel.
摘要：
遗传性视神经病变是由视网膜神经节细胞的变性引起的，视网膜神经节细胞的轴突形成视神经，具有一致的遗传异质性。作为我们诊断活动的一部分,我们对2186例疑似遗传性视神经病变的患者进行了Leber遗传性视神经病变突变检测和87种核基因外显子测序的联合回顾性评估.Leber遗传性视神经病变检测的阳性诊断率为18％（199/1126个指标），92%(184/199)携带线粒体DNA的三种主要致病变体之一(m.11778G>A,66.5%；m.3460G>A，15%和m.14484T>C，11%）。常染色体显性或隐性视神经病变的阳性诊断率为27％（451/1680指数病例），10个基因一起占这个队列的96%。这代表30%的总体阳性诊断率。确定的前10个核基因包括OPA1，WFS1，ACO2，SPG7，MFN2，AFG3L2，RTN4IP1，TMEM126A，NR2F1和FDXR。11个额外的基因,每个案件占不到1%，在17个人中被确认。我们的结果表明，10个主要基因占我们核基因组诊断病例的96％以上。
