title: Olfaction in Parkin single and compound heterozygotes in a cohort of young onset Parkinson's disease patients.
abstract: BACKGROUND
  Parkin related Parkinson's disease (PD) is differentiated from idiopathic PD by absent or sparse Lewy bodies, and preserved olfaction. The significance of single Parkin mutations in the pathogenesis of PD is debated.
  
  
  OBJECTIVE
  To assess olfaction results according to Parkin mutation status. To compare the prevalence of Parkin single heterozygous mutations in patients diagnosed with PD to the rate in healthy controls in order to establish whether these single mutations could be a risk factor for developing PD.
  
  
  METHODS
  Parkin gene mutation testing was performed in young onset PD (diagnosed <50 years old) to identify three groups: Parkin homozygous or compound heterozygote mutation carriers, Parkin single heterozygote mutation carriers, and non-carriers of Parkin mutations. Olfaction was tested using the 40-item British version of the University of Pennsylvania smell identification test (UPSIT).
  
  
  RESULTS
  Of 344 young onset PD cases tested, 8 (2.3%) were Parkin compound heterozygotes and 13 (3.8%) were Parkin single heterozygotes. Olfaction results were available in 282 cases (eight compound heterozygotes, nine single heterozygotes, and 265 non-carriers). In Parkin compound heterozygotes, the median UPSIT score was 33, interquartile range (IQR) 28.5-36.5, which was significantly better than in single Parkin heterozygotes (median 19, IQR 18-28) and non-carriers (median score 22, IQR 16-28) (ANOVA P < 0.001). These differences persisted after adjusting for age, disease duration, gender, and smoking (P < 0.001). There was no significant difference in UPSIT scores between single heterozygotes and non-carriers (P = 0.90).
  
  
  CONCLUSIONS
  Patients with Parkin compound heterozygous mutations have relatively preserved olfaction compared to Parkin single heterozygotes and non-carriers. The prevalence of Parkin single heterozygosity is similar to the 3.7% rate reported in healthy controls.
authors.affiliation: Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK. nmalek@nhs.net.
authors.forename: N
authors.initials: N
authors.lastname: Malek
authors.affiliation: Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: D M A
authors.initials: DM
authors.lastname: Swallow
authors.affiliation: Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Grosset
authors.affiliation: School of Social & Community Medicine, University of Bristol, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Lawton
authors.affiliation: Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Smith
authors.affiliation: Queen's Medical Centre, Nottingham, UK.
authors.forename: N P
authors.initials: NP
authors.lastname: Bajaj
authors.affiliation: Clinical Neurosciences, John van Geest Centre for Brain Repair, Cambridge, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Barker
authors.affiliation: School of Social & Community Medicine, University of Bristol, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bresner
authors.affiliation: Institute of Neuroscience, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Burn
authors.affiliation: Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Foltynie
authors.affiliation: Department of Clinical Neurosciences, University College London, UK.
authors.forename: H R
authors.initials: HR
authors.lastname: Morris
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
authors.forename: N
authors.initials: N
authors.lastname: Williams
authors.affiliation: Department of Molecular Neuroscience, University College London, UK.
authors.forename: N W
authors.initials: NW
authors.lastname: Wood
authors.affiliation: Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Grosset
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D015995:Prevalence; D012903:Smell / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Parkin; Parkinson's disease; University of Pennsylvania Smell Identification test; genetics; olfaction