Department of Ophthalmology, University of Western Ontario, London, Ontario, Canada.
Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada.
Can J Neurol Sci. 2023 Sep;50(5):738-744. doi: 10.1017/cjn.2022.279. Epub 2022 Jul 27.
Leber hereditary optic neuropathy (LHON) is a rare but bilaterally blinding disease. Three characteristic disease-causing point mutations, and other less common mutations, are most often found on the mitochondrially encoded genes of NADH-ubiquinone oxidoreductase core subunits (MT-ND). The purpose of this study is to provide an overview of LHON mutations in Southwestern Ontario and to describe the associated demographic and clinical characteristics.
A retrospective genetic and clinical chart review was performed from January 2015 to 2020. Patients were identified within a mitochondrial mutation database and included if a mutation was detected on the MT-ND1, -ND4, or -ND6 genes. A clinical chart review was done on all available patients.
Forty-five of 63 patients identified had classic disease-causing mutations (6.7% m.3460G>A, 44.4% m.11778G>A, and 48.9% m.14484T>C). Several of the remaining 18 patients had rare mutations previously documented in association with LHON. Of the 14 patients with clinical charts accessible for review, 12 had symptomatic disease, and all but one had bilateral optic neuropathies. Nine patients had classic LHON mutations and 3 had possible novel mutations; 7 were males; 9 had final visual acuity ≤ 20/200 in at least one eye; and 6 of those had ≤20/400 in both eyes.
This study adds to the literature on LHON in Canada, and specifically Southwestern Ontario. The demographic and clinical data regarding LHON in this geographic location, as well as possible novel disease-causing mutations, provide important information to aid clinicians in recognizing cases of LHON that may otherwise be disregarded.
Leber 遗传性视神经病变（LHON）是一种罕见但可致双侧失明的疾病。三种特征性致病点突变以及其他不太常见的突变，最常发生在线粒体编码的 NADH-泛醌氧化还原酶核心亚基（MT-ND）的基因上。本研究旨在概述安大略省西南部的 LHON 突变，并描述相关的人口统计学和临床特征。
对 2015 年 1 月至 2020 年的遗传和临床图表进行回顾性研究。从线粒体突变数据库中确定患者，如果在 MT-ND1、-ND4 或 -ND6 基因上检测到突变，则将其纳入研究。对所有可用患者进行临床图表审查。
在确定的 63 名患者中，有 45 名患者存在典型的致病突变（6.7% m.3460G>A，44.4% m.11778G>A，48.9% m.14484T>C）。其余 18 名患者中的几名患者存在先前与 LHON 相关的罕见突变。在可查阅临床图表的 14 名患者中，有 12 名患有症状性疾病，且所有患者除 1 例外均患有双侧视神经病变。9 名患者存在经典 LHON 突变，3 名患者可能存在新的突变；7 名男性；9 名患者至少一眼的最终视力≤20/200；其中 6 名患者双眼视力均≤20/400。
本研究增加了加拿大，特别是安大略省西南部 LHON 的文献。该地理位置的 LHON 人口统计学和临床数据，以及可能的新致病突变，为临床医生识别可能被忽视的 LHON 病例提供了重要信息。
