Phenotypic variability of parkin mutations in single kindred.
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.


CONCLUSIONS
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.
Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and The University of Sydney, St. Leonards, New South Wales, Australia.
Brianada
B
Koentjoro
Jin-Sung
JS
Park
Ainhi Duy
AD
Ha
Carolyn M
CM
Sue
D000368:Aged; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein