TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea

Authors

  • Gabor G. Kovacs MD, PhD,

    1. Institute of Neurology, Medical University of Vienna, Vienna, Austria
    2. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
    3. National Institute of Psychiatry and Neurology, Budapest, Hungary
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  • Jill R. Murrell PhD,

    1. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • Sandor Horvath MD, PhD,

    1. Department of Neurology, Ferenc Flor Hospital, Kistarcsa, Hungary
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  • Laszlo Haraszti MD, PhD,

    1. Department of Psychiatry, Ferenc Flor Hospital, Kistarcsa, Hungary
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  • Katalin Majtenyi MD, PhD,

    1. National Institute of Psychiatry and Neurology, Budapest, Hungary
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  • Maria J. Molnar MD, PhD,

    1. Clinical and Research Centre for Molecular Neurology, Semmelweis University, Budapest, Hungary
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  • Herbert Budka MD, MScDhc,

    1. Institute of Neurology, Medical University of Vienna, Vienna, Austria
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  • Bernardino Ghetti MD,

    1. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • Salvatore Spina MD

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
    2. Department of Neurological, Neurosurgical and Behavioral Sciences, University of Siena, Siena, Italy
    • Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Medical Science Building A134, 635 Barnhill Drive, Indianapolis, Indiana 46202
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  • Potential conflict of interest: None reported.

Abstract

TDP-43 has been identified as the pathological protein in the majority of cases of frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). TARDBP mutations have so far been uniquely associated with familial and sporadic ALS. We describe clinicopathological and genetic findings in a carrier of the novel K263E TARDBP variation, who developed frontotemporal dementia, supranuclear palsy, and chorea, but no signs of motor neuron disease. Neuropathologic examination revealed neuronal and glial TDP-43-immunoreactive deposits, predominantly in subcortical nuclei and brainstem. This is the first report of a TARDBP variation associated with a neurodegenerative syndrome other than ALS. © 2009 Movement Disorder Society

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