Leber病14484原发合并新继发位点突变频谱研究

Mutations spectrum of mitochondrial DNA 14484 mutations combined with other secondary mutations with Leber hereditary optic neuropathy

目的:分析中国人Leber遗传性视神经病变14484位点突变的频谱及其遗传特征。方法:针对57例疑似LHON 14484位点突变的患者设计引物进行PCR扩增,PCR产物用限制性片段长度多态性(RFLP)和单链构象多态性(SSCP)并联合DNA测序的方法进行分析。同时选取20例正常健康成人作为对照。结果:57例LHON疑似14484位点突变者中,确诊9例为14484位点突变,占15.8%。其中2例单纯性14484位点突变,占22.2%;3例14484位点联合14502位点突变,占33.3%;3例14484位点联合14470位点突变,占33.3%;1例14484位点联合14569位点突变,占11.1%。对照组正常健康成人测序结果均为正常序列。结论:中国人线粒体LHON14484原发性位点突变中,存在与其他继发性位点联合致病的倾向,其中以14484+14502和14484+14470这两个突变位点为主。

Objective： To analyze the 14484 mutation of Leber hereditary optic neuropathy（LHON） and the clinical features in Chinese patients.Methods：57 patients suspected of having LHON 14484 mutation were detected by polymerase chain reaction（PCR）,single strand conformation polymorphism reaction（SSCP）,restriction fragment length polymorphisms（RFLP） and measurement of DNA sequence had been done for PCR products.20 healthy adults were selected as control.Results：In the 57 patients suspected of having LHON,mtDNA14484 mutation was found in 9 probands（15.8%）,including 2 patients with 14484 mutation（22.2%）,3 patients with 14484 and 14502 mutations（33.3%）,3 patients with 14484 and 14470 mutations（33.3%）,1 patient with 14484 and 14569 mutations（11.1%）.The results of measurement of DNA sequence for normal healthy adults were normal.Conclusion：In the LHON patients of mtDNA 14484 mutation in Henan,China,there is a tendency of the primary 14484 mutation and second mutations simultaneously,the mutations of 14484 ＋ 14502 and 14484 ＋ 14470 are main.Research on spectrum of the primary mtDNA mutation and second mutations in LHON is developed,it is of the significance to the risk factors of the disease occurred,risk prediction,diagnosis and prevention.