【摘要】 目的揭示一个Leber遗传性视神经病变(Leber’s hereditary optic neuropathy,LHON)家系的遗传基础。方法对家系成员提取线粒体DNA(mtDNA),直接进行测序分析,用分子克隆法为每个人构建单克隆群,再用高分辨熔解曲线技术和DNA测序的方法,对家系中成员的单克隆群分析统计,计算该家系成员的线粒体DNA突变比例。结果该家系患者mtDNA上11778位核苷酸发生G到A的突变。家系成员中G11778A突变比例分别为:先证者(II2)91.67%;父亲(I2)0%;3位母系家属正常人依次为:(I1)90.83%、(II1)53.16%、(II3)49.16%。结论 G11778A的同质体(即:突变比例达到90%以上)女性仍可不患Leber遗传性视神经病变,该女性后代的平均突变比例远小于先前的报道。更多还原

【Abstract】 Objective To investigate the genetic basis for a Chinese pedigree with Leber’s hereditary optic neuropathy(LHON).Methods Direct DNA sequence was performed for 3 candidate mtDNA sites.High resolution melting and sequencing were carried out to analyse the proportion of mutant mtDNA of each member in the LHON pedigree afterwards.Results A single nucleotide substitution of G for A was found at 11778th of mtDNA.The proportion of mtG11778A for the proband(II2),his father(I2),and three unaffected maternal members(I1,II1,II3) were 91.67%,0%,90.83%,53.16%,49.16%,respectively.Conclusion Our study found that the female G11778A mtDNA mutation carrier I1,who contains more than 90% G11778A mtDNA mutation,could be unaffected,and her children’s average proportion of mutant mtDNA was far lower than the previous reports.更多还原