Complex relationship between Parkin mutations and Parkinson disease

Am J Med Genet. 2002 Jul 8;114(5):584-91. doi: 10.1002/ajmg.10525.


Mutations in the Parkin gene cause juvenile and early onset Parkinsonism. While Parkin-related disease is presumed to be an autosomal-recessive disorder, cases have been reported where only a single Parkin allele is mutated and raise the possibility of a dominant effect. In this report, we re-evaluate twenty heterozygous cases and extend the mutation screening to include the promoter and intron/exon boundaries. Novel deletion, point and intronic splice site mutations are described, along with promoter variation. These data, coupled with a complete review of published Parkin mutations, confirms that not only is recessive loss of Parkin a risk factor for juvenile and early onset Parkinsonism but that Parkin haplo-insufficiency may be sufficient for disease in some cases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Alternative Splicing / genetics
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Humans
  • Introns / genetics
  • Ligases / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic / genetics
  • Review Literature as Topic
  • Sequence Deletion
  • Ubiquitin-Protein Ligases*


  • DNA
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Ligases