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

Authors

  • Madeleine E. Sharp MD,

    Corresponding author
    1. Department of Neurology, Columbia University, New York, USA
    • Correspondence to: Dr. Madeleine E. Sharp, 710 West 168th Street, Neurological Institute, 3rd floor, New York, NY 10032, USA; ms4567@columbia.edu

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  • Karen S. Marder MD, MPH,

    1. Department of Neurology, Columbia University, New York, USA
    2. Gertrude H. Sergievsky Center, Columbia University, New York, USA
    3. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA
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  • Lucien Côté MD,

    1. Department of Neurology, Columbia University, New York, USA
    2. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA
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  • Lorraine N. Clark PhD,

    1. Department of Molecular Genetics, Columbia University, New York, USA
    2. Department of Pathology, Columbia University, New York, USA
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  • William C. Nichols PhD,

    1. Division of Human Genetics, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Jean-Paul Vonsattel MD,

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA
    2. Department of Pathology, Columbia University, New York, USA
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  • Roy N. Alcalay MD, MSc

    1. Department of Neurology, Columbia University, New York, USA
    2. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA
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  • Funding agencies: This study was supported by NS036630 grant and the Parkinson's Disease Foundation. Genotyping and clinical testing was funded by R56NS036630, NIH/NIA 5P50AG08702, NIH 2UL1RR024156 and the Parkinson's Disease Foundation.

  • Relevant conflicts of interest/financial disclosures: Madeleine E. Sharp received fellowship funding from Parkinson Society Canada and from the Parkinson's Disease Foundation.

  • Full financial disclosures and author roles may be found in the online version of this article.

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. © 2013 International Parkinson and Movement Disorder Society

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