Phenotypic variability of parkin mutations in single kindred

Mov Disord. 2012 Sep 1;27(10):1299-303. doi: 10.1002/mds.25041. Epub 2012 Jul 17.


Background: Mutations in parkin have been associated with autosomal recessive early-onset Parkinson's disease (PD). Here, we report on unusual phenotypic variability within a family with mutations in parkin.

Methods: The proband and her parents were clinically assessed. Mutation analysis was performed using genomic DNA and complementary DNA. The protein expression of Parkin and Mitofusin 2 was examined by western blotting.

Results: The proband was a compound heterozygote with no detectable Parkin and presented with early-onset PD. The father, a single heterozygote with reduced expression of Parkin, had mild loss of arm swing. The mother, who had only very mild rigidity, was unexpectedly found to be a homozygote with no Parkin expression. The proband, but not the parents, met the Queen Square Brain Bank criteria for PD. Parkin-dependent ubiquitination of Mitofusin 2 was impaired in the mother and the proband.

Conclusion: We report the first case of a homozygous mutation carrier in parkin who had no functional protein and only mild signs of parkinsonism in her seventh decade, whereas her daughter developed typical early-onset PD. This family demonstrates phenotypic variability in parkin-related parkinsonism. © 2012 Movement Disorder Society.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • DNA Mutational Analysis
  • Family Health*
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Mutation / genetics*
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Skin / pathology
  • Ubiquitin-Protein Ligases / genetics*
  • Young Adult


  • Ubiquitin-Protein Ligases
  • parkin protein