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

Madeleine E. Sharp*, Karen S. Marder, Lucien Côté, Lorraine N. Clark, William C. Nichols, Jean Paul Vonsattel, Roy N. Alcalay

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)566-568
Number of pages3
JournalMovement Disorders
Volume29
Issue number4
DOIs
StatePublished - Apr 2014
Externally publishedYes

Funding

FundersFunder number
National Institute on Aging
National Institutes of Health2UL1RR024156, 5P50AG08702
National Institute of Neurological Disorders and StrokeR56NS036630

    Keywords

    • Lewy bodies
    • Neuropathology
    • Parkin
    • Parkinson's disease

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