Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations.
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.
Wu
Ruey-Meei
RM
Department of Neurology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Shan
Din-E
DE
Sun
Chen-Ming
CM
Liu
Ren-Shyan
RS
Hwu
Wuh-Liang
WL
Tai
Chun-Hwei
CH
Hussey
Jennifer
J
West
Andrew
A
Gwinn-Hardy
Katrina
K
Hardy
John
J
Chen
Judy
J
Farrer
Matt
M
Lincoln
Sarah
S
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
D012333:RNA, Messenger; D017661:Receptors, Presynaptic; D019788:Fluorodeoxyglucose F18; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases; D004298:Dopamine