Zhu D P, Economou E P, Antonarakis S E, Maumenee I H
Johns Hopkins Center for Hereditary, Eye Disease of the Wilmer Ophthalmological Institute, Baltimore, Maryland 21205.
Am J Med Genet. 1992 Jan 15;42(2):173-9. doi: 10.1002/ajmg.1320420208.
Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by bilateral acute or subacute loss of central vision, primarily in young males. A G----A single base mutation at 11778nt of the mitochondrial genome which eliminates a SfaNI restriction site [Wallace et al., 1988; Holt et al., 1989; Hotta et al., 1989; Singh et al., 1989; Vilkki et al., 1989; Yoneda et al., 1989; Stone et al., 1990; Lott et al., 1990.] has been found in more than 60% of the families with LHON studied. We studied 25 persons from 4 families with LHON using SfaNI and Mae III digestion of a 201 base pair polymerase chain reaction (PCR) product encompassing the 11778nt mutation. The loss of the SfaNI site and the acquisition of a Mae III site at 11778nt were identified in all maternal relatives of the LHON families studied. The mutation was heteroplasmic in all affected individuals, female carriers, and males at-risk. The heteroplasmy of mitochondrial DNA (mtDNA) was also identified by direct DNA sequencing of PCR amplified by direct DNA sequencing of PCR amplified mtDNA digested by SfaNI or Mae III. It appears that the proportion of the mutant mtDNA correlates with the severity of the disease.
Leber遗传性视神经病变（LHON）是一种母系遗传疾病，其特征为双侧急性或亚急性中心视力丧失，主要发生在年轻男性中。线粒体基因组11778nt处的G----A单碱基突变消除了一个SfaNI限制性酶切位点[Wallace等人，1988年；Holt等人，1989年；Hotta等人，1989年；Singh等人，1989年；Vilkki等人，1989年；Yoneda等人，1989年；Stone等人，1990年；Lott等人，1990年]，在超过60%接受研究的LHON家族中被发现。我们使用SfaNI和Mae III对包含11778nt突变的201碱基对聚合酶链反应（PCR）产物进行酶切，对4个LHON家族的25人进行了研究。在所研究的LHON家族的所有母系亲属中，均鉴定出11778nt处SfaNI位点的缺失和Mae III位点的获得。该突变在所有受影响个体、女性携带者和有患病风险的男性中均为异质性。通过对经SfaNI或Mae III酶切的PCR扩增线粒体DNA（mtDNA）进行直接DNA测序，也鉴定出了mtDNA的异质性。似乎突变型mtDNA的比例与疾病的严重程度相关。
