Study On Parkin Gene In Patients With Early-onset And Late-onset Parkinson Disease

Although most of Parkinson disease (PD) patients are sporadic cases, it is reported that there are 16% PD patients whose first-degree relatives also suffer from PD. Recently, some autosomal dominant and autosomal recessive PD families were described, and 2 familial PD associated gene, a-synuclein and parkin were discovered. There is an agreement that autosomal recessive juvenile parkinsonism(AR-JP) is a monogenic disease caused by mutation in parkin gene. This study was designed to analyze the parkin mutation in early-onset and late-onset PD patients.Materials and MethodsVenous blood was obtained from 44 PD patients who were admitted to the Second Affiliated hospital of Medical college, Zhejiang University, from May 2000 to Jan 2001. The patients were divided into 2 groups: EOP(early-onset Parkinson disease) group with onset age<40, 17 cases, 9 males, 8 females, with onset age between 25-40, mean 34.4+4.3 years; LOP (late-onset Parkinson disease) group with onset age>40, 27 cases, 18 males, 9 females, with onset age between 41-72, mean 52.5+9.2 years. In them, there were 4 patients that were all from EOP group, whose brother or sister were also afflicted with PD. Genomic DNA was extracted from venous blood and parkin mutation was analyzed by polymerase chain reaction (PCR), agarose electrophoresis and single strand conformation polymorphism (SSCP).ResultOut of 17 EOF, 1 patient had Exon3 and ExonS combined deletions; and of 27 LOP, 1 patient had ExonS deletion. No point mutation was detected by SSCP. Besides, among 4 familial patients, 1(25%) had parkin deletions, while among 40 non-familial patients only 1(2.5%) had parkin deletion.DiscussionDeletion mutations in parkin gene can be detected in patients with EOF as well as LOP. Two mutations that has been found would lead to shift mutation in parkin gene or to a truncated parkin protein, which will damage the normal function of parkin protein and give rise to the accumulation of abnormal protein substance. It leads to cells death in Substantia Nigra and then results in the absence of pigment neuron in Substantia Nigra pathologically and parkinsonism clinically. This study suggests that parkin mutation rate in EOF patients in our country is lower than that in European countries. Parkinsonism caused by parkin mutation may initiate at a later age. Parkin mutation is related to heritage, especially to autosomal recessive heritage PD.