Parkinson's disease with Lewy bodies associated with a heterozygous PARKIN dosage mutation

Background PARKIN-related disease remains incompletely understood. First, the pathogenicity of heterozygous PARKIN mutations is unclear, although some evidence supports causality. Second, unlike sporadic Parkinson's disease (PD), Lewy bodies are present only in a minority of cases. Only one other heterozygote PARKIN carrier with autopsy findings has been described. Our case adds to the broadening pathological and clinical phenotype of PARKIN-related disease. Methods Clinical chart, genetic analysis, and pathological findings of a patient with familial PD are reviewed. Results A 44-year-old man developed slowly progressive tremor-predominant PD with excellent response to levodopa. Genetic analysis revealed a heterozygous PARKIN exon 3-4 deletion, also present in 2 family members with early-onset PD. Postmortem examination showed severe neuronal loss in the substantia nigra and nucleus coeruleus with the presence of diffuse Lewy bodies. Conclusions The deletion is unlikely an incidental finding considering family history, age at onset, and the presence of clinical and pathological features not typical of sporadic PD. (c) 2013 International Parkinson and Movement Disorder Society