Department of Neurology (SC, HJ, JP, JW, XZ), Beijing Tongren Hospital, Capital Medical University, Beijing, China; and Medical Research Center (LY, JS), Beijing Tongren Hospital, Capital Medical University, Beijing, China.
J Neuroophthalmol. 2020 Mar;40(1):30-36. doi: 10.1097/WNO.0000000000000799.
The primary aim of this study was to describe clinical features of Chinese sporadic Leber hereditary optic neuropathy (LHON) caused by rare primary mitochondrial DNA (mtDNA) mutations.
We characterized a Chinese patient cohort with rare primary mtDNA mutations at Beijing Tongren Hospital between 2015 and 2018. The clinical features of these patients were retrospectively recorded and analyzed.
Sixteen patients with LHON who had the selected rare primary mutations, including m.4171C>A (3 patients), m.10197G>A (1 patient), m.14459G>A (4 patients), and m.14502T>C (8 patients), were evaluated. The mean age at disease onset was 15 ± 6 years, and the male to female ratio was 15:1. Of 32 eyes of all patients, 75% (24/32) had a worst Snellen best-corrected visual acuity ≤0.1 (worse than 20/200), while 67% (2/3) who were carrying the m.4171C>A mutation experienced significant visual improvement. In addition, 40% (2/5) of patients with LHON carrying only m.14502T>C mutation had only mild visual impairment. Isolated manifestations of LHON was present in 94% (15/16) of all patients; 1 patient with the m.14459G>A mutation had LHON plus dystonia. Brain MRI T2 short tau inversion recovery sequences demonstrated optic atrophy in 62.5% (10/16); increased T2 signal in the optic nerve was found in 38% (6/16) of patients. The patient with LHON plus dystonia demonstrated optic atrophy and increased T2 signal in basal ganglia.
Patients with LHON and rare primary mutations have diverse clinical phenotypes. Those with the m.4171C>A mutation are more likely to have a good visual prognosis, while the m.14502T>C mutation may play a synergistic role in disease onset. Increased signal in the optic nerve on MRI is not rare, and this feature should not exclude LHON as the potential cause for optic neuropathy.
本研究的主要目的是描述中国散发型莱伯遗传性视神经病变（LHON）患者中罕见原发性线粒体 DNA（mtDNA）突变的临床特征。
我们对 2015 年至 2018 年在北京同仁医院就诊的罕见原发性 mtDNA 突变的中国患者队列进行了特征描述。回顾性记录并分析了这些患者的临床特征。
评估了 16 例携带所选罕见原发性突变的 LHON 患者，包括 m.4171C>A（3 例）、m.10197G>A（1 例）、m.14459G>A（4 例）和 m.14502T>C（8 例）。发病时的平均年龄为 15±6 岁，男女比例为 15：1。所有患者的 32 只眼中，75%（24/32）的最佳矫正视力最差 Snellen 视力≤0.1（差于 20/200），而携带 m.4171C>A 突变的患者中 67%（2/3）视力显著改善。此外，仅携带 m.14502T>C 突变的 LHON 患者中 40%（2/5）仅有轻度视力障碍。所有患者中 94%（15/16）表现为孤立性 LHON，1 例 m.14459G>A 突变患者同时存在 LHON 伴肌张力障碍。脑 MRI T2 短 tau 反转恢复序列显示 62.5%（10/16）的患者存在视神经萎缩；38%（6/16）的患者视神经 T2 信号增加。同时患有 LHON 和肌张力障碍的患者显示出视神经萎缩和基底节区 T2 信号增加。
携带罕见原发性突变的 LHON 患者具有不同的临床表型。携带 m.4171C>A 突变的患者更有可能具有良好的视力预后，而 m.14502T>C 突变可能在发病中起协同作用。MRI 上视神经信号增加并不少见，这种特征不应排除 LHON 是视神经病变的潜在原因。
