title: Parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism.
abstract: BACKGROUND
  parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage.
  
  
  METHODS
  We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and > or = 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons.
  
  
  RESULTS
  Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations.
  
  
  CONCLUSIONS
  Anticipation is not linked to parkin, and may signify a distinct disease entity.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA. pips@u.washington.edu
authors.forename: Parvoneh
authors.initials: P
authors.lastname: Poorkaj
authors.forename: Lina
authors.initials: L
authors.lastname: Moses
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Montimurro
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: Haydeh
authors.initials: H
authors.lastname: Payami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020132:Anticipation, Genetic; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
references.citation: Arch Neurol. 2002 Oct;59(10):1622-30
references.pmid: 12374501
references.citation: Am J Med Genet. 2002 Jul 8;114(5):584-91
references.pmid: 12116199
references.citation: Neurology. 2003 Mar 11;60(5):796-801
references.pmid: 12629236
references.citation: Ann Neurol. 2003 May;53(5):624-9
references.pmid: 12730996
references.citation: Mov Disord. 2003 Apr;18(4):425-9
references.pmid: 12671950
references.citation: Mov Disord. 2003 Nov;18(11):1306-11
references.pmid: 14639672
references.citation: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references.pmid: 1564476
references.citation: Neurology. 1994 Oct;44(10):1978-9
references.pmid: 7936260
references.citation: Neurology. 1995 Jan;45(1):135-8
references.pmid: 7824103
references.citation: Ann Neurol. 1995 Sep;38(3):373-8
references.pmid: 7668822
references.citation: Nature. 1998 Apr 9;392(6676):605-8
references.pmid: 9560156
references.citation: N Engl J Med. 2000 May 25;342(21):1560-7
references.pmid: 10824074
references.citation: Ann Neurol. 2000 Jul;48(1):65-71
references.pmid: 10894217
references.citation: Ann Neurol. 2000 Aug;48(2):245-50
references.pmid: 10939576
references.citation: Neurology. 2000 Sep 26;55(6):800-5
references.pmid: 10993999
references.citation: Neurol Sci. 2001 Feb;22(1):73-4
references.pmid: 11487208
references.citation: Neurology. 2001 Sep 11;57(5):924-7
references.pmid: 11552035
references.citation: Ann Neurol. 2001 Sep;50(3):293-300
references.pmid: 11558785
references.citation: Ann Neurol. 2001 Dec;50(6):812-5
references.pmid: 11761482
references.citation: Neurology. 2002 Apr 23;58(8):1239-46
references.pmid: 11971093
references.citation: J Neurol Sci. 2003 Mar 15;207(1-2):11-7
references.pmid: 12614925