title: Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations.
abstract: We report on clinical (18)F-labeled 6-fluorodopa ((18)F-dopa) positron emission tomography (PET) and molecular genetic analyses of an ethnic Chinese family in which three siblings presented with early-onset Parkinson's disease. As described in some parkin patients, neither sleep benefit nor diurnal fluctuation was noted. Interestingly, depression, anxiety, and obsessive-compulsive disorders were manifest. The (18)F-dopa PET scans showed bilateral presynaptic dopaminergic dysfunction without marked lateralization. Molecular genetic analysis showed identical chromosome 6 haplotypes inherited by affected subjects, with alternate allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified aberrantly spliced parkin transcripts, suggesting that unusual parkin protein isoforms may be expressed in the brain and retain some function.
authors.affiliation: Department of Neurology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
authors.forename: Din-E
authors.initials: DE
authors.lastname: Shan
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Sun
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Chun-Hwei
authors.initials: CH
authors.lastname: Tai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hussey
authors.forename: Andrew
authors.initials: A
authors.lastname: West
authors.forename: Katrina
authors.initials: K
authors.lastname: Gwinn-Hardy
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Judy
authors.initials: J
authors.lastname: Chen
authors.forename: Matt
authors.initials: M
authors.lastname: Farrer
authors.forename: Sarah
authors.initials: S
authors.lastname: Lincoln
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000503:physiopathology; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D004292:Dominance, Cerebral / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006239:Haplotypes; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D011699:Putamen / Q000000981:diagnostic imaging / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D017661:Receptors, Presynaptic / Q000502:physiology; D013624:Taiwan; D014055:Tomography, Emission-Computed; D044767:Ubiquitin-Protein Ligases
chemical_list: D012333:RNA, Messenger; D017661:Receptors, Presynaptic; D019788:Fluorodeoxyglucose F18; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases; D004298:Dopamine