Leber遗传性视神经病变中风险因素的研究进展

Research progress of risk factors of Leber’s hereditary optic neuropathy

Leber遗传性视神经病变(LHON)是一种典型的母系遗传性眼病,主要累及视网膜和巩膜筛板前部视盘黄斑束纤维,且具有男性高发及不完全外显的特点。该病以线粒体DNA原发突变m.11778G>A、m.14484T>C和m.3460G>A为致病分子基础,同时存在其他风险因素共同作用影响其表型表达,如线粒体DNA继发突变、线粒体单倍体型、核修饰基因、雌激素、维生素B12和环境因素等。目前LHON的分子诊断主要聚焦于线粒体DNA原发突变位点的检测,存在相对局限性,因此综合解析多种风险因素,构建多维度的疾病预防和诊疗系统,为患者提供精准化和个体化医疗服务,将为减缓LHON疾病进程和降低发病率起到重要作用,也为LHON发病机制的不同角度深入研究和临床干预策略提供新思路。

Leber’s hereditary optic neuropathy(LHON)is a paradigm maternal hereditary eye disease,mainly involving the retinal and macular fibers of the optic disc in the anterior ethmoid plate of the sclera.LHON has the characteristics of sex bias among males and incomplete penetrance.Primary mitochondrial DNA mutations m.11778G>A,m.14484T>C,m.3460G>A are the molecular basis of LHON.However,other risk factors,such as secondary mitochondrial DNA mutations,mitochondrial haplotypes,nuclear modification genes,estrogen,vitamin B12 and environmental factors,work together to affect its phenotypic expression.The clinical diagnosis of LHON mainly limited to the detection of the primary mutation site of mitochondrial DNA.Therefore,comprehensive analysis of multiple risk factors of LHON will facilitate to construct multi-dimensional model of prevention,diagnosis and treatment system,which provide accurate and individualized medical services for patients.These may alleviate the incidence in LHON families.It also provides new ideas and different angles for the in-depth study of the pathogenesis of LHON.