散发性早发帕金森病PARK2基因突变及其临床特征

Mutation of PARK2 gene in sporadic early-onset Parkinson′s disease and its clinical characteristics

目的探讨42例散发性早发性帕金森病(EOPD)PARK2基因突变情况及突变患者的临床特点。方法采用SYBR GreenI实时荧光定量以及DNA直接测序方法,对42例EOPD患者进行PARK2基因突变分析。结果在42例EOPD患者中共发现5例PARK2基因突变,外显子杂合缺失突变、外显子纯合双重重复突变、复合杂合点突变各1例,另外2例存在相同的杂合小片段缺失突变。c.850G>C和c.968-973delGTGTCC为已经报道的突变,c.925G>T为未报道新突变。PARK2基因突变EOPD患者发病年龄比无PARK2基因突变者小。但是在统一帕金森病评定量表(UPDRS)3.0版第Ⅲ部分关期评分和Hoehr-Yahr关期评分上无差异。结论散发性EOPDPARK2基因突变率为11.9%;点突变是散发性EOPD的主要突变类型;PARK2基因突变组和无突变组的EOPD患者在临床症状上和病情严重程度上无明显差异,但PARK2基因突变组发病年龄小,病程长,病情进展缓慢。

Objective To investigate PARK2 gene mutations in 42 patients with sporadic early-onset Parkinson＇s disease （EOPD） and to explore their clinical characteristics. Methods A total of 42 sporadic EOPD patients were screened for mutations in PARK2 gene by using SYBR GreenI real-time PCR and DNA direct sequencing methods. Results 5 patients carried PARK2 gene mutations in the 42 sporadic EOPD, including 1 heterozygous deletions mutation, 1 homo- zygous duplication mutation, 1 compound heterozygous point mutation and 2 identical heterozygous small sequence dele- tion mutations. Two of the mutations （ c. 850G 〉 C and c. 968-973delGTGTCC） were reported previously. The c. 925G 〉 T was a novel mutation. The patients with PARK2 mutations showed an earlier onset age than those without PARK2 mutations. But they showed no significant difference in the score of UPDRS （Unified Parkinson＇s Disease Rating Scale） 3.0 and Hoehr-Yahr. Conclusion The frequency of mutations in PARK2 gene is 11.9% in sporadic EOPD. Point mu- tation is the main type of mutations in sporadic EOPD. There are no significant differences in clinical features and dis- ease severiies between patients with or without PARK2 mutations. However, patients who carry PARK2 mutations showa significantly earlier onset age, longer disease duration and slower progression than those without PARK2 mutations.