title: Parkin disease: a clinicopathologic entity?
abstract: OBJECTIVE
  Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss.
  
  
  OBJECTIVE
  To investigate whether parkin-linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD).
  
  
  METHODS
  We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison.
  
  
  RESULTS
  Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex).
  
  
  CONCLUSIONS
  These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.
authors: Reta Lila Weston Institute for Neurological Studies, University College London, London, England.
authors: Karen M
authors: KM
authors: Doherty
authors: Laura
authors: L
authors: Silveira-Moriyama
authors: Laura
authors: L
authors: Parkkinen
authors: Daniel G
authors: DG
authors: Healy
authors: Michael
authors: M
authors: Farrell
authors: Niccolo E
authors: NE
authors: Mencacci
authors: Zeshan
authors: Z
authors: Ahmed
authors: Francesca M
authors: FM
authors: Brett
authors: John
authors: J
authors: Hardy
authors: Niall
authors: N
authors: Quinn
authors: Timothy J
authors: TJ
authors: Counihan
authors: Timothy
authors: T
authors: Lynch
authors: Zoe V
authors: ZV
authors: Fox
authors: Tamas
authors: T
authors: Revesz
authors: Andrew J
authors: AJ
authors: Lees
authors: Janice L
authors: JL
authors: Holton
mesh_terms: D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000145:classification / Q000235:genetics / Q000473:pathology; D012720:Severity of Illness Index; D014015:Tissue Banks; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein