Yen M Y, Yen T C, Pang C Y, Liu J H, Wei Y H
Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, ROC.
Invest Ophthalmol Vis Sci. 1992 Jul;33(8):2561-6.
Leber's hereditary optic neuropathy (LHON) causes acute or subacute central visual loss in healthy young males. Recently, it has been thought to be caused by a single nucleotide change in the ND4 gene in the mitochondrial genome. Mitochondrial DNA (mtDNA) of leukocytes and hair follicle cells from five patients in four families with LHON and nine relatives were analyzed by Sfa NI and Mae III enzyme digestion and DNA sequencing. Loss of Sfa NI site was found in all patients and maternal lineages but not in nonmaternal lineages and normal controls. Mae III digested all the mtDNAs that lost the Sfa NI site. The restriction fragment pattern of polymerase chain reaction (PCR) products exhibited mtDNA heteroplasmy in the hair follicle cells but not in blood cells of the proband in one family. Direct sequencing of PCR-amplified mtDNA fragments encompassing the ND4 gene of the patients disclosed a transition from guanine to adenine at nucleotide position 11778. These results confirm previous reports that a G to A point mutation is associated with LHON and that tissue variability and heteroplasmy of mtDNA exist in some, but not all, LHON patients.
Leber遗传性视神经病变（LHON）可导致健康年轻男性出现急性或亚急性中枢性视力丧失。最近，人们认为它是由线粒体基因组中ND4基因的单个核苷酸变化引起的。通过Sfa NI和Mae III酶切及DNA测序，对来自4个患有LHON的家族的5名患者及9名亲属的白细胞和毛囊细胞的线粒体DNA（mtDNA）进行了分析。在所有患者及其母系家族中均发现Sfa NI位点缺失，而非母系家族和正常对照中未发现。Mae III酶切了所有失去Sfa NI位点的mtDNA。在一个家族中，先证者的毛囊细胞中聚合酶链反应（PCR）产物的限制性片段模式显示出线粒体DNA异质性，而血细胞中未显示。对患者包含ND4基因的PCR扩增mtDNA片段进行直接测序，发现在核苷酸位置11778处有一个从鸟嘌呤到腺嘌呤的转变。这些结果证实了先前的报道，即G到A的点突变与LHON相关，并且在部分（而非全部）LHON患者中存在mtDNA的组织变异性和异质性。
