三个常染色体隐性遗传早发型帕金森病家系的PARKIN基因研究

目的 探讨PARKIN基因与中国人常染色体隐性遗传早发型帕金森病（autosomal recessive early-onset Parkinson’s disease，AREP）家系的关系。方法 对3个AREP家系的6例患者和23位成员进行系统的临床检查并进行PARKIN基因PCR扩增，产物通过变性高压液相色谱（denaturing high—performance liquid chmnatogmphy，DHPLC）进行突变检测，阳性结果标本进行基因测序。结果 所有研究对象的PARKIN基因外显子均扩增成功。DHPLC检测和基因测序发现一个家系中存在PARKIN基因杂合Gly284Arg突变，另一个家系中存在PARKIN基因Ser167Asn多态性，且患者均有环境毒物接触史。结论 PARKIN基因杂合Gly284Arg突变在环境因素的协同作用下可能导致发病。PARKIN基因Ser167Asn多态性是帕金森病的易感因素，汞中毒与其共同作用可能导致发病。

A study on PARKIN gene in three pedigrees with autosomal recessive early-onset Parkinson's disease

Objective To detect the possible relationship between PARKIN gene and the Chinese pedigree with autosomal recessive early-onset Parkinson's disease(AREP). Methods Clinical examination was carried out in 6 patients from 3 Chinese pedigrees with AREP and their 23 family members. PCR amplification of all exons of PARKIN gene was performed. The PCR products were analyzed by denaturing high-performance liquid chromatography(DHPLC) to screen for point mutation and polymorphism. And in the samples with abnormal DHPLC result , further sequencing was conducted to confirm the type of mutation and polymorphism. Results All exons of PARKIN gene from the research subjects were successfully amplified. A heterozygous point mutation (Gly284Arg) in exon 7 was found in one pedigree. A polymorphism (Ser167Asn) in exon 4 was found in another pedigree. All the patients had the past history of exposure to environmental poison. Conclusion When acting together with risky environmental factors, the heterozygous mutation Gly284Arg in PARKIN gene may cause AREP. The polymorphism Ser167Asn in PARKIN gene increases the risk of developing Parkinson's disease and may cause AREP when acting together with hydrargyrism.