We conducted an updated epidemiological study of Leber hereditary optic neuropathy (LHON) in Australia by using registry data to establish the risk of vision loss among different LHON mutations, sex, age at onset, and mitochondrial haplogroup. We identified 96 genetically unrelated LHON pedigrees, including 56 unpublished pedigrees, and updated 40 previously known pedigrees, comprising 620 affected individuals and 4,948 asymptomatic carriers. The minimum prevalence of vision loss due to LHON in Australia in 2020 was one in 68,403 individuals. Although our data confirm some well-established features of LHON, the overall risk of vision loss among those with a LHON mutation was lower than reported previously—17.5% for males and 5.4% for females. Our findings confirm that women, older adults, and younger children are also at risk. Furthermore, we observed a higher incidence of vision loss in children of affected mothers as well as in children of unaffected women with at least one affected brother. Finally, we confirmed our previous report showing a generational fall in prevalence of vision loss among Australian men. Higher reported rates of vision loss in males with a LHON mutation are not supported by our work and other epidemiologic studies. Accurate knowledge of risk is essential for genetic counseling of individuals with LHON mutations. This knowledge could also inform the detection and validation of potential biomarkers and has implications for clinical trials of treatments aimed at preventing vision loss in LHON because an overestimated risk may lead to an underpowered study or a false claim of efficacy.

我们通过使用注册数据来确定不同 LHON 突变、性别、发病年龄和线粒体单倍群的视力丧失风险，对澳大利亚的 Leber 遗传性视神经病变 (LHON) 进行了最新的流行病学研究。我们确定了 96 个与基因无关的 LHON 谱系，包括 56 个未发表的谱系，并更新了 40 个先前已知的谱系，包括 620 名受影响的个体和 4,948 名无症状携带者。2020 年澳大利亚因 LHON 导致视力丧失的最低患病率为 68,403 人中的 1 人。尽管我们的数据证实了 LHON 的一些公认特征，但 LHON 突变患者视力丧失的总体风险低于之前报告的——男性为 17.5%，女性为 5.4%。我们的研究结果证实，女性、老年人和年幼的儿童也处于危险之中。此外，我们观察到受影响母亲的子女以及至少有一个受影响兄弟的未受影响妇女的子女视力丧失的发生率更高。最后，我们证实了我们之前的报告，该报告显示澳大利亚男性视力丧失的流行率逐代下降。我们的工作和其他流行病学研究不支持具有 LHON 突变的男性报告的更高的视力丧失率。准确了解风险对于 LHON 突变个体的遗传咨询至关重要。这些知识还可以为潜在生物标志物的检测和验证提供信息，并对旨在预防 LHON 视力丧失的治疗的临床试验产生影响，因为高估的风险可能导致研究效力不足或疗效的虚假声明。