Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by subacute optic atrophy which results in severe visual impairment. The penetrance, clinical expression and disease onset are variable, and frequently associated with other extraocular symptoms. The disease phenotype remains to be an intriguing question which is dependent upon primary as well as secondary mtDNA mutations. In this study we analyzed the whole mtDNA sequence in six LHON families from Serbian population. The mtDNA sequencing was performed by Sanger's method and various bioinformatic tools were used for analysis of detected mutations. LHON patients carry all three (m.3460G>A, m.11778G>A and m.14484T>C) primary mutations, together with numerous secondary mtDNA mutations. Four novel mutations (m.4516G>A, m.8779C>T, m.13138G>A and m.15986insG) in four different families were discovered. The m.8779C>T and m.13138G>A mutations could have a potential influence on LHON symptoms, but the issue of effect of secondary mtDNA mutations in LHON patients needs to be better clarified in future studies.

中文翻译：

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Leber遗传性视神经病变家族继发性mtDNA突变分析：四种新变异及其与临床表现的关联

Leber 遗传性视神经病变 (LHON) 是一种以亚急性视神经萎缩为特征的线粒体疾病，可导致严重的视力障碍。外显率、临床表现和疾病发作是可变的，并且经常与其他眼外症状相关。疾病表型仍然是一个有趣的问题，它取决于原发性和继发性 mtDNA 突变。在这项研究中，我们分析了来自塞尔维亚人群的六个 LHON 家族的整个 mtDNA 序列。mtDNA 测序采用 Sanger 方法进行，并使用各种生物信息学工具对检测到的突变进行分析。LHON 患者携带所有三种（m.3460G>A、m.11778G>A 和 m.14484T>C）初级突变，以及许多次级 mtDNA 突变。四个新突变（m.4516G>A、m.8779C>T、m.13138G> A 和 m.15986insG) 在四个不同的家族中被发现。m.8779C>T 和 m.13138G>A 突变可能对 LHON 症状有潜在影响，但 LHON 患者继发性 mtDNA 突变的影响问题需要在未来的研究中更好地阐明。