180例散发性神经变性病引起的痴呆朊蛋白基因突变的研究

目的对180例散发性神经变性病引起的痴呆患者进行朊蛋白基因（PRNP）突变的筛查，探讨PRNP基因突变在临床诊断的神经变性病痴呆中的发生情况以及可能的原因。方法研究180例散发性痴呆患者和310例健康对照的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4个不同的PRNP基因杂合突变，分别为$97N、F198V、R208C和M232R，突变率2．22％，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4例突变可能为病理性突变。结论4例突变中有3例为新突变，4例突变均可能与痴呆的发生相关。

Analysis of prion protein gene mutation in 162 patients with Alzheimer's disease caused by sporadic neurodegenerative dementias

Objective To evaluate the frequency of prion protein （PRNP） gene mutations and their correlation with clinical phenotypes in sporadic neurodegenerative dementias, and explore the mutation rate of PRNP gene in clinically diagnosed Alzheimer＇s disease （AD） and the possible mechanism involved. Methods The study objects were consisted of 180 sporadic neurodegenerative dementias 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 Four different missense mutations of PRNP gene were detected in 180 sporadic neurodegenerative dementias, S97N.F198V 、R208C and M232R, which were not found in 310 normal controls. The mutation rate is 2.22%. Combined with the clinical phenotypes, the four mutations may be pathogenic. Conclusions Three out of the four mutations are novel. Combined with the clinical data, the PRNP mutations may be associated with dementia.