title: Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an 18F-dopa PET study.
abstract: PARK6, a locus for early-onset recessive parkinsonism, has been causally implicated in nine unrelated families from four different countries. The gene is still unidentified and hence the importance of PARK6 as a cause of Parkinson's disease is unknown. To date, no pathology or functional imaging studies are available on PARK6-linked parkinsonism. We have used (18)F-dopa positron emission tomography to study four patients who are homozygous and three asymptomatic relatives who are heterozygous for PARK6. The clinically affected PARK6 subjects had a similar 85% reduction in posterior dorsal putamen (18)F-dopa uptake to a group of idiopathic Parkinson's disease patients matched for clinical disease severity and duration but showed significantly greater involvement of head of caudate and anterior putamen. The group of asymptomatic PARK6 carriers showed a significant mean 20 to 30% reduction in caudate and putamen (18)F-dopa uptake in comparison with controls, individual values falling toward the bottom of the normal range. Our results indicate that PARK6 pathology results in a more uniform loss of striatal dopamine terminal function than Parkinson's disease. The subclinical loss of striatal dopamine storage capacity found in the PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect.
authors.affiliation: Department of Molecular Pathogenesis, Institute of Neurology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Naheed L
authors.initials: NL
authors.lastname: Khan
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Alberto
authors.initials: A
authors.lastname: Albanese
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Paola
authors.initials: P
authors.lastname: Piccini
mesh_terms: D000328:Adult; D000368:Aged; D004298:Dopamine / Q000235:genetics / Q000502:physiology*; D005260:Female; D005462:Fluorine Radioisotopes; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D018709:Statistics, Nonparametric; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D005462:Fluorine Radioisotopes; D005819:Genetic Markers; D004298:Dopamine