title: Evaluation of 50 probands with early-onset Parkinson's disease for Parkin mutations.
abstract: BACKGROUND
  Early onset PD has been associated with different mutations in the Parkin gene, including exon deletions and duplications.
  
  
  METHODS
  The authors performed an extensive mutational analysis on 50 probands with onset of PD at younger than 50 years of age. Thirteen probands were ascertained from a registry of familial PD and 37 probands by age at onset at younger than 50 years, blind to family history. Mutational analysis was undertaken on the probands and available family members and included conventional techniques (single strand conformation polymorphism analysis and sequencing) and a newly developed method of quantitative duplex PCR to detect alterations of gene dosage (exon deletions and duplications) in PARKIN:
  
  
  RESULTS
  Using this new technique, the authors detected eight alterations of gene dosage in the probands, whereas 12 mutations were found by conventional methods among the probands and another different mutation in an affected family member. In total, the authors identified compound heterozygous mutations in 14%, heterozygous mutations in 12%, and no Parkin mutation in 74% of the 50 probands. We expanded the occurrence of Parkin mutations to another ethnic group (African-American).
  
  
  CONCLUSIONS
  The authors systematically screened all 12 Parkin exons by quantitative PCR and conventional methods in 50 probands. Eight mutations were newly reported, 2 of which are localized in exon 1, and 38% of the mutations were gene dosage alterations. These results underline the need to screen all exons and to undertake gene dosage studies. Furthermore, this study reveals a frequency of heterozygous mutation carriers that may signify a unique mode of inheritance and expression of the Parkin gene.
authors.affiliation: Department of Neurology, Medical University of Lübeck, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hedrich
authors.forename: K
authors.initials: K
authors.lastname: Marder
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Kann
authors.forename: T
authors.initials: T
authors.lastname: Lynch
authors.forename: H
authors.initials: H
authors.lastname: Meija-Santana
authors.forename: P P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: E
authors.initials: E
authors.lastname: Schwinger
authors.forename: S B
authors.initials: SB
authors.lastname: Bressman
authors.forename: S
authors.initials: S
authors.lastname: Fahn
authors.forename: C
authors.initials: C
authors.lastname: Klein
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases