Screening the three LHON primary mutations in the general Chinese population by using an optimized multiplex allele-specific PCR
Screening the three LHON primary mutations in the general Chinese population by using an optimized multiplex allele-specific PCR
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DOI：
10.1016/j.cca.2010.06.026
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发表时间：
2010-11-11
影响因子：
5
通讯作者：
Yao, Yong-Gang
中科院分区：
文献类型：
--
作者：
Bi, Rui;Zhang, A-Mei;Yao, Yong-Gang
研究背景Leber遗传性视神经病变（Leber hereditary optic neuropathy，LHON）是最常见的线粒体疾病之一，主要由线粒体DNA（mitochondrial DNA，mtDNA）的3个突变（m.3460G>A、m.11778G>A和m.14484T>C）引起。这些无症状携带者具有重要的临床意义，因为她们是潜在的未来患者，并且女性携带者可以将致病突变传递给她们的后代。因此，在一般人群中筛查LHON的三个主要突变对遗传咨询具有重要意义。方法我们在前人研究的基础上优化了一种多重等位基因特异性PCR方法，应用该方法对1571例无视神经病变症状或家族史的中国普通人群进行了LHON 3个原发突变的筛查。PCR方法可以检测到m.3460G>A的异质性水平为5%、5%和20%。m 11778G>A和m 14484T>C。分别1571例受试者中均未检出3种WON原发突变。结论3种LHON原发突变在中国人群中较为罕见。优化的MAS-PCR检测方法为3种LHON原发突变的检测提供了一种简便、快速、经济的方法，可用于临床诊断。
Background Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial diseases, which is mainly caused by three mitochondrial DNA (mtDNA) mutations (m.3460G>A, m 11778G>A and m.14484T>C). Incomplete penetrance suggests that there might be asymptomatic carriers in general populations These asymptomatic carriers are clinically important as they are potential future patients and the female carriers could transfer the pathogenic mutations to their offspring. Thus, screening the three LHON primary mutations in general populations is important for genetic counselingMethods We optimized a multiplex allele-specific PCR method based on previous studies, and the sensitivity was evaluated The three LHON primary mutations were screened by using this MAS-PCR method in 1571 subjects from general Chinese populations that are without symptoms or family history of optic neuropathyResults The optimized MAS-PCR approach can detect a heteroplasmy level at 5%, 5%, and 20% for m.3460G>A. m 11778G>A and m 14484T>C. respectively. None of the three WON primary mutations was detected in the 1571 subjectsConclusion The three LHON primary mutations are rare in general Chinese populations The optimized MAS-PCR assay provides an easier, faster and more cost-effective method for detection of the three LHON primary mutations, making it practical for clinical diagnosis (C) 2010 Elsevier BV All rights reserved