Phenotypic variability of parkin mutations in single kindred

Abstract 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