162例散发性阿尔茨海默病朊蛋白基因突变的研究

目的:在162例散发性阿尔茨海默病(Alzheimer's disease,AD)患者中进行朊蛋白基因(PRNP)突变的筛查,探讨PRNP基因突变在临床诊断的AD中的发生情况以及可能的原因。方法:研究对象包括162例散发性AD患者和310例健康对照。对研究对象的PRNP基因的开放阅读框架进行PCR扩增,产物直接测序,异常者重复测序,并与对照组对比。结果:共发现3个不同的PRNP基因杂合突变,分别为S97N、F198V和R208C,突变率1.85%,结合患者的临床表型,以及未在310个正常人中发现突变,考虑这3例突变可能为病理性突变。结论:3例突变均为新突变,可能与痴呆的发生相关。

Prion Protein Gene Analysis in 162 Patients of Alzheimer's disease

Objective：To detect the role of PRNP gene mutations in sporadic Alzheimer＇s disease（AD） and evaluate the mutation rate of PRNP gene in clinically diagnosed AD.Methods：The study group consisted of 162 sporadic AD patients and 310 normal controls.Genomic DNA was extracted from peripheral blood leucocytes of all subjects followed by in vitro amplification using polymerase chain reaction（PCR）.The PCR products were directly sequenced by Sanger method.Results：We detected three different missense mutations of PRNP gene in 162 sporadic AD：S97N、F198V and R208C,which were not found in 310 normal controls.The mutation rate is 1.85%.Combined with the clinical phenotypes,the three mutations are probably pathogenic.Conclusion：All of the three mutations are novel.Combined with the clinical data,the PRNP mutations in the 3 patients may be associated with dementia.