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POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe

Authors

  • Julia Schicks MD,

    1. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, and German Research Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany
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    • Julia Schicks and Matthis Synofzik contributed equally to this work.

  • Matthis Synofzik MD,

    1. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, and German Research Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany
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    • Julia Schicks and Matthis Synofzik contributed equally to this work.

  • Claudia Schulte,

    1. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, and German Research Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany
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  • Ludger Schöls MD

    Corresponding author
    1. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, and German Research Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany
    • Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Hoppe-Seyler-Str. 3, University of Tübingen, Tübingen 72076, Germany
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  • Potential conflict of interest: Nothing to report.

Abstract

Nuclear genes, in particular mitochondrial polymerase gamma (POLG) and PEO1, have been increasingly recognized to cause mitochondrial diseases. Both genes assume a complementary role as part of the mitochondrial DNA (mtDNA) replication fork and, accordingly, seem to present with largely overlapping phenotypical spectra. We assessed the frequency and phenotypic spectrum of PEO1 compared to POLG mutations in a cohort of 80 patients with cerebellar ataxia for which common repeat expansion diseases had been excluded. Patients were selected to present additional features previously described for PEO1 mutations, namely early age of onset, progressive external ophthalmoplegia (PEO), or epilepsy. Whereas PEO1 mutations were not found in our cohort, POLG frequently caused ataxia with PEO (47%), psychiatric comorbidities (20%) and, more rarely, with epilepsy (14%). Thus, PEO1 is rare in Central Europe even in those patients displaying characteristic phenotypic features. In contrast, POLG is rather common in Central European ataxia patients. It should be particularly considered in ataxia patients with PEO, psychiatric comorbidities, and/or sensory neuropathy, even if characteristic mitochondrial extra-CNS features are absent. © 2010 Movement Disorder Society.

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