目的 分析3个中国Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)家系的临床和分子遗传学特点.方法 收集临床诊断为LHON的3个中国汉族家系.对3个家系的先证者进行眼科相关检查,PCR扩增3个原发位点G3460A、G11778A、T14484C所在的线粒体ND1、ND4、ND6基因.并对3个先证者线粒体基因组全序列进行PCR扩增.结果 3个家系先证者的视力损伤程度不同,外显率分别12.5％、11.1％和33.3％.3个家系先证者及母系成员均未携带ND1 G3460A、ND4G11778A、ND6 T14484C这3个常见原发位点,但均携带同质性ND1 T3866C突变.线粒体ND1 3866位点T＞C碱基的改变使线粒体复合体Ⅰ ND1亚基跨膜区的第187位进化高度保守的非极性异亮氨酸转变为极性苏氨酸.结论 线粒体ND1 T3866C突变可能与LHON相关.%Objective To report on the clinical,genetic and molecular characteristics of three ethnic Han Chinese families affected with Leber's hereditary optic neuropathy (LHON).Methods The three families were all diagnosed with LHON.Ophthalmologic examinations were conducted on the probands.The ND1,ND4 and ND6 genes of the mitochondrial DNA (mtDNA) were amplified with PCR respectively for the screening of three primary mutations G3460A,G11778A and T14484C.The entire mtDNA of the probands were also amplified by PCR.Results Analysis of mtDNA in the three pedigrees has failed to find the presence of the three LHON associated mutations but presence of a homoplastic ND1 T3866C mutation in all probands and their matrilineal relatives.The probands had different levels of visual impairment.The penetrance in the three families has been calculated as 12.5％,11.1％ and 33.3％,respectively.The T3866C mutation has resulted in replacement of isoleucine at position 187 with theronine.The isoleucine at position 187 is located at one of the transmembrane domains of ND1 polypeptide.Conclusion Above results have suggested that the ND1 T3866C mutation might have been involved in the pathogenesis of LHON in the three Chinese families studied.
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