Leber遗传性视神经病三个家系患者线粒体DNA突变位点的研究

目的对Leber遗传性视神经病（Leber’s hereditary optic neuropathy，LHON）家系的原发突变位点11778与继发突变位点9804、13708、13730、15257进行突变分析，探讨两者之间相关性及对LHON的影响。方法应用聚合酶链反应一单链构象多态性和DNA测序对3个LHON家系37位母系成员和47名正常人的线粒体DNA（mitochondrial DNA，mtDNA）进行检测。结果16例患者及其母系亲属均存在11778位点突变，未发现9804、13708、13730、15257位点突变，但DNA测序发现13759、13928、13942、15301、15326、15323这6个新突变位点。结论3个家系都存在mtDNA11778位点突变，在13759位点患者突变率远高于正常人，差异有统计学意义（P〈0．001），表明13759是LHON新的继发突变位点。

Study on five point mutations in mitochondrial DNA in patients with Leber''''s hereditary optic neuropathy

Objective To analyze the relationship between the primary mutation at np11778 and the secondary mutations at np9804, np13708, np13730, np15257 in three Chinese pedigrees with Leber's hereditary optic neuropathy (LHON) and to detect the effects of the mutations on LHON. Methods Thirty-seven maternal individuals from three LHON pedigrees and forty-seven normal controls were involved in this study. Polymerase chain reaction-single-strand conformation polymorphism(PCR-SSCP) and DNA sequencing were used to detect the mutations in mitochondrial DNA (mtDNA). Results All patients and their maternal relatives had the np11778 mtDNA primary mutation. None had the secondary mutations at np9804, np13708 and np13730 and np15257. DNA sequencing of the PCR fragment revealed six new point mutations at np13759, np13928, np13942, np15301, np15323 and np15326. Conclusion All three Chinese pedigrees with LHON had the mtDNA11778 primary mutation .The frequency of mutation at np13759 in Chinese patients with LHON is higher than that in normal Chinese controls. These findings idicate that np13759 is a new secondary mutation of LHON in Chinese.