线粒体ND1基因在Leber遗传性视神经病变中的作用

Leber 遗传性视神经病变（LHON）是一种典型的眼科母系遗传性疾病，主要累及青年男性，患者之间常呈现不同程度的视力损伤。三个线粒体DNA原发突变（G11778A，G3460A 和T14484C）是其发病的主要分子基础。本研究的主要目的是研究线粒体ND1基因在Leber遗传性视神经病变中的作用。本研究拟在收集的1000多例LHON 汉族家系基础上，进行LHON 相关线粒体基因新突变筛查，筛选与LHON相关的ND1基因新突变位点，绘制线粒体ND1基因在中国人群LHON中的突变频谱；评估线粒体ND1 G3635A突变及新位点在LHON突变细胞中的作用，揭示G3635A突变及新位点在LHON中的致病机制，进而阐明线粒体ND1基因在Leber遗传性视神经病变中的作用。

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited eye disease that generally affects young adults with the rapid, painless, bilateral loss of central vision. Mutations in mitochondrial DNA (mtDNA) are the molecular bases for this disorder. The ND1 G3460A, ND4 G11778A, and ND6 T14484C mutations is the primary mutation. Typical features in LHON pedigrees are incomplete penetrance and male bias among the affected subjects.Therefore, other modifier factors including environmental factors, nuclear, and mitochondrial genetic modifiers should modulate the phenotypic manifestation of visual impairment. In order to investigate the pathophysiology of mitochondrial ND1 gene in Leber’s hereditary optic neuropathy. We performed the clinical, genetic evaluation and complete mitochondrial genome sequence analysis of 1000 Han Chinese pedigrees. Screening new mutation of ND1 gene and building the mitochondrial ND1 gene mutation spectrum; assess mitochondrial ND1 G3635A mutation and other new sites in mutant cells, revealing ND1 G3635A mutation and other new sites in LHON pathogenic mechanisms, and thus clarify the pathophysiology of mitochondrial ND1 gene in Leber’s hereditary optic neuropathy.