title: Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study.
abstract: Molecular and clinical characterization of parkin-associated parkinsonism is well described; however, there are no data available on progression of dopamine terminal dysfunction in parkin-associated disease. We have used [(18)F]dopa PET serially to study members of a family with young-onset parkinsonism who are compound heterozygous for mutations in the parkin gene, having an exonic deletion and a novel intronic splice site mutation. Four patients have been studied twice, 10 years apart, to assess disease progression. Additionally, we have studied five asymptomatic family members, four of whom carry a single parkin mutation and one individual who has a normal genotype. Two of the carriers and the individual with the normal genotype had repeat [(18)F]dopa PET. The group of parkin patients showed a significantly slower loss of putamen [(18)F]dopa uptake (P = 0.0008) compared with a group of idiopathic Parkinson's disease (IPD) patients who had baseline putamen [(18)F]dopa uptake and disease severity similar to the parkin group. These results indicate that disease progression in patients with parkin mutations is slower than that of IPD patients. The group of asymptomatic parkin carriers also showed significant striatal dopaminergic dysfunction, and three of them developed subtle extrapyramidal signs. However, the two carriers scanned twice showed no progression over a 7-year period. The slower rate of disease progression in parkin patients may explain the near normal longevity of these patients with young onset parkinsonism.
authors.affiliation: MRC Clinical Sciences Centre, and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Naheed L
authors.initials: NL
authors.lastname: Khan
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Nicola
authors.initials: N
authors.lastname: Pavese
authors.forename: Mary G
authors.initials: MG
authors.lastname: Sweeney
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Paola
authors.initials: P
authors.lastname: Piccini
mesh_terms: D000328:Adult; D000368:Aged; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D018709:Statistics, Nonparametric; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data; D044767:Ubiquitin-Protein Ligases
chemical_list: D005462:Fluorine Radioisotopes; D004295:Dihydroxyphenylalanine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases