Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt.
Genes (Basel). 2020 Sep 2;11(9):1037. doi: 10.3390/genes11091037.
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder that affects central vision in young adults and is typically associated with mitochondrial DNA (mtDNA) mutations. This study is based on a mutational screening of entire mtDNA in eight Serbian probands clinically and genetically diagnosed with LHON and four of their family members, who are asymptomatic mutation carriers. All obtained sequence variants were compared to human mtDNA databases, and their potential pathogenic characteristics were assessed by bioinformatics tools. Mitochondrial haplogroup analysis was performed by MITOMASTER. Our study revealed two well-known primary LHON mutations, m.11778G>A and m.3460G>A, and one rare LHON mutation, m.8836A>G. Various secondary mutations were detected in association with the primary mutations. MITOMASTER analysis showed that the two well-known primary mutations belong to the R haplogroup, while the rare LHON m.8836A>G was detected within the N1b haplogroup. Our results support the need for further studies of genetic background and its role in the penetrance and severity of LHON.
Leber 遗传性视神经病变(LHON)是一种母系遗传疾病,影响年轻人的中心视力,通常与线粒体 DNA(mtDNA)突变有关。本研究基于对 8 名塞尔维亚先证者的整个 mtDNA 的突变筛查,这些先证者在临床上和遗传上被诊断为 LHON,他们的 4 名无症状突变携带者是他们的家庭成员。所有获得的序列变体都与人类 mtDNA 数据库进行了比较,并通过生物信息学工具评估了它们潜在的致病特征。线粒体单倍群分析由 MITOMASTER 进行。我们的研究揭示了两种众所周知的原发性 LHON 突变,m.11778G>A 和 m.3460G>A,以及一种罕见的 LHON 突变 m.8836A>G。与原发性突变相关,检测到各种继发性突变。MITOMASTER 分析表明,这两种众所周知的原发性突变属于 R 单倍群,而罕见的 LHON m.8836A>G 则存在于 N1b 单倍群中。我们的研究结果支持进一步研究遗传背景及其在 LHON 的外显率和严重程度中的作用的必要性。