12例散发性早发性痴呆朊蛋白基因变异的研究

目的研究12例散发性早发性痴呆患者伴有锥体外系和(或)小脑、额叶症状]朊蛋白基因的变异。方法从患者外周血白细胞中提取基因组DNA,用多聚酶链式反应(PCR)进行朊蛋白基因的体外扩增,再用Sanger法对PCR产物进行测序分析,测序发现的变异用限制性片断长度多态性方法(RFLP)进行进一步确认。结果在12例患者中发现4种不同的朊蛋白基因杂合性变异:M 129V、E 219K、M 232R和五串联重复序列内的24个核苷酸缺失(de lR 2),其中M 232R可能是病理性突变,其余3种为基因多态性。结论与既往朊蛋白基因变异的研究相结合,考虑朊蛋白基因多态性在日本人群中相对常见,而且与朊蛋白基因突变有关的基因型-表现型的异质性关系为深入理解早发性痴呆的病因提供了新的启发。

Prion protein gene variations in 12 cases with sporadicearly onset dementia

Objective To investigate prion protein gene variations in 12 Japanese patients affected by sporadic early onset dementia with either extrapyramidal or cerebellar or frontal symptom. Methods After obtaining informed consent from all subjects,genomic DNA was extracted from peripheral blood leucocytes followed by in vitro amplification using polymerase chain reaction(PCR).The PCR products were directly sequenced by Sanger method using an automated fluorescent sequencer.PCR and restriction fragment length polymorphism(PCR-RFLP)analysis was carried out to further confirm the variations by comparing with normal control. Results We identified a total of 4 different variations in PRNP gene heterozygously:a 24-nucleotide deletion,ATG to GTG at codon 129(M129V),GAG to AAG at codon 219(E219K)and ATG to AGG at codon 232(M232R).The first three variations were belong to polymorphism,but M232R was probably pathogenic. Conclusion Taken together with previous investigations of PrP gene variations,PrP gene polymorphisms may be relatively common in Japanese populations.And there is a heterogeneous genotype-phenotype correlation in PrP gene mutation.PrP gene mutation may give further insight into early-onset dementia.