title: Early-onset Parkinson's disease in a Chinese population: 99mTc-TRODAT-1 SPECT, Parkin gene analysis and clinical study.
abstract: Early Onset Parkinson's Disease (EOPD) is characterized by selective degeneration of nigrostriatal dopaminergic neurons and a marked response to levodopa. However, at present, few methods are available as diagnostic tools for EOPD except for 18F-DOPA PET. In addition, little is known about the correlation between clinical severity, neuroimaging grading and genetic susceptibility. In the present study, 99mTc-TRODAT-1 SPECT and brain MRI were used to identify 30 cases of non-familial EOPD from a Chinese cohort of 230. All 30 PD patients had an age of onset of less than 55 years (mean age at onset, 41.5+/-9.3 years). Each of the 30 EOPD cases was sub-classified into one of five stages based on the 99mTc-TRODAT-1 SPECT findings. In the early stages of PD (stages 1 and 2), a lower uptake of 99mTc-TRODAT-1 in the putamen was found, while uptake in the caudate nucleus was normal. In the latter stages (stages 3, 4, 5), 24 patients revealed a diffuse and uniform loss of 99mTc-TRODAT-1 uptake in the putamen and the caudate nucleus. Further, in conventional genetic studies of the 30 patients, six novel mutations were found in the Parkin gene, and these included five heterozygous point mutations (C441R, Q311H, V258M, C212G, and S193I) and one homozygous deletion (exon 10-12). Known polymorphisms (Ser167Asn, Val380Leu) were also found in a number of patients. However, gene dosage analysis did not reveal any compound heterozygous mutations in these 30 patients using quantitative duplex PCR. This is the first study to examine EOPD patients of Chinese ethnic background (not exhibiting a definite familial trait), to offer a complete genetic analysis of the Parkin gene, and to correlate clinical stages of the disease with dopamine re-uptake.
authors.affiliation: Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Chiang
authors.forename: Cheng-Yoong
authors.initials: CY
authors.lastname: Pang
authors.forename: Shin-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Yue-Loong
authors.initials: YL
authors.lastname: Hsin
authors.forename: Peterus
authors.initials: P
authors.lastname: Thajeb
authors.forename: Yih-Jing
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People; D002421:Caudate Nucleus / Q000000981:diagnostic imaging; D050483:Dopamine Plasma Membrane Transport Proteins; D017353:Gene Deletion; D006801:Humans; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000502:physiology; D015609:Organotechnetium Compounds; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000208:ethnology / Q000235:genetics*; D017354:Point Mutation; D011699:Putamen / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein