摘要
目的筛查Leber遗传性视神经病变(Leberhereditaryopticneuropathy,LHON)患者的线粒体DNA碱基突变,研究LHON的临床发病特点及分子生物学改变。方法对3个疑似LHON家系进行调查,知情同意后,抽取了30个母系成员的血样,对照组32个血样均来自无视力障碍的正常人。采用聚合酶链反应扩增结合单链构象多态性分析对3个家系的30个母系成员的线粒体DNA(mtDNA)进行了11个位点的突变筛查。结果3个家系的母系成员共41人(男23人,女19人),发病20例,发病率48·78%,男女比例3∶1,平均发病年龄28.73岁。3个家系患者发病年龄随传代数的增加而减小,呈现遗传早发现象。含11778、11696两个位点的片段1,实验组30例检测结果全部为异常,对照组32例单链构象多态性检测结果全部正常。含14459、14482、14484、14498位点的片段2实验组30例中仅有1例检测结果为异常,对照组32例SSCP检测结果全部正常。含3394、3460两个位点的片段3和含4136、4160、4216三个位点的片段4,实验组和对照组的所有样本均未发现异常。结论LHON患者发病年龄随传代数的增加而提前,具有遗传早发现象;综合国内的文献资料和我们的研究结果,我国LHON患者以携带11778点突变占绝大多数;所检测3个家系母系成员有共同的突变位点,但只有部分发病,其中已发病者可确诊为LHON患者,未发病的母系成员为该病的携带者。
Objective To screen mtDNA mutations of Leber hereditary optic neuropathy,and to investigate the clinical characteristics and cell biological alternation of the disease. Methods Three pedigrees were inquired and 30 maternal members of them were tested. Following informed consent, periphery blood samples were obtained. Thirty-two healthy persons without optic disease were included in control group. Total DNA was isolated using routine way. Four mtDNA fragments were amplified using four pairs of primers, which covered eleven nucleotide position mutations reported abroad. Then the product was analysed by single strand conformation polymorphism analysis. Results There were 41 blood species members in the three pedigrees including 23 male and 19 female. Fifteen males and 5 females were affected. Compared with control group, single stranth conformation polymorphism analysis of polymerase chain reaction products amplified with primer pair 1 in the experiment group, showed bands shift in all lanes, only one lane showed band shift in products amplified with primer pair 2, and no band shift was found in products amplified with primer pair 3 and 4. Conclusion The age of onset was ahead of schedule with increasing passing generation within these pedigrees; Nucleotide position 11 778 mutation is overwhelming majority of Leber hereditary optic neuropathy patients in China;All materal members in these three pedigrees carry same mtDNA mutation. Only a part of them have been affected. Members with symptoms are Leber hereditary optic neuropathy patients and their asymptomatic maternal relatives are carriers.
出处
《眼科新进展》
CAS
2006年第5期361-363,368,共4页
Recent Advances in Ophthalmology
