Mutation Analysis Of Parkin Gene In Sporadic Early-onset Parkinson’s Disease And Clinical Characteristics Discussion

ObjectiveParkinson’s disease (PD) is a common neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra,The classical clinical features of the disease are resting tremor, rigidity, bradykinesia, and postural instability and have a prevalence of more than1%among persons older than65years of age.Early-onset Parkinson’s disease (EOPD) generally refers to the age of onset<50years of PD patients, accounting for about10%of PD patients.Although the etiology of PD has not been fully elucidated,the causative genes of PD (PARK1-PARK18) have been found gradually, the importance of genetic factor in PD is under the spotlight recently.According to the study,the causative gene PARK2(parkin) is closely related to EOPD,and has a high detection rate in EOPD.There are two types of mutation in parkin gene,point mutation or small sequence mutation and exon rearrangements mutation.Currently, the research of parkin gene mutation in sporadic EOPD is overflow in domestic and overseas, but relevant studys combined gene phenotypes with clinic features are still lack. In our research,we did mutation analysis of parkin gene in42sporadic EOPD patiets and to explore the clinical characteristics of patients with mutation.Methods1、According to the following criteria,A total of42sporadic EOPD patients were enrolled in the study from January2010to June2011in the Department of Neurology,Qilu Hospital:1、The diagnosis was confirmed using the UK Parkinson’s Disease Brain Bank Criteria..2、an age at onset of<50years3、with no family history.The patients were all from Shandong Province.2、A total of42sporadic EOPD was screened for mutation in parkin gene using SYBR GreenI real-time PCR and DNA direct sequencing.According to the patient for parkin gene mutations,42sporadic EOPD patients were divided into parkin mutations group and no parkin mutations group, the two groups were compared the similarities and differences in clinical manifestations and analysis the clinic features of mutations group.3、The data were analyzed between parkin mutations group and no parkin mutations group with Mann-Whitney U test and t-test by SPSS13.0. P<0.05was considered statistically significant. Results1、 Five patients carried parkin gene mutations in42sporadic EOPD, including1heterozygous deletions mutation,1homozygous duplication mutation,1compound heterozygous point mutation and2identical small sequence deletion mutation. Two of the mutations(c.850G>C and c.968-973delGTGTCC) were reported previously.The c.925G>T was a novel mutation.In addition,we also found six known Polymorphisms,including c.500G>A、c.1054G>C、c.1012O＞T、c.933+5G>A、 c.*15O＞A、c.171+25G＞T2、The patients with parkin mutation showed ealier onset age (z=2.89, p<0.05) and longer disease duration (z=2.36,p<0.05) than those without parkin mutation. But those two showed no significant difference in the score of UPDRS(Unified Parkinson’Disease Rating Scale)3.0and Hoehr-Yahr (p>0.05). It is accounted for that there are no significant difference in clinical symptoms and disease severity.Conclusions1、The frequency of mutation in parkin gene is11.9%with sporadic EOPD.2、Point mutation may be the main type of mutation. 3、Heterozygous mutation of parkin gene is a risk factor of PD,which leads to EOPD together with environmental factors.4、There are no significant differences in clinical features and disease severity between patients with parkin mutation and those without.However,patients who carry parkin mutation show a significantly earlier onset age,longer disease duration and slower progression than those who without parkin mutation.