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Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage

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Abstract

Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG repeat or polyglutamine diseases. Recent morphological studies characterized the pathoanatomical features in heterozygous SCA2 patients and revealed severe neuronal loss in a large variety of cerebellar and extra-cerebellar brain sites. In the present study, we examined the brain pathoanatomy of a monozygous twin of a large Hungarian SCA2 family with pathologically extended CAG repeats in both SCA2 alleles. This unique patient was in the initial clinical stage of SCA2 and died almost 3 years after SCA2 onset. Upon pathoanatomical investigation, we observed loss of giant Betz pyramidal cells in the primary motor cortex, degeneration of sensory thalamic nuclei, the Purkinje cell layer, and deep cerebellar nuclei, as well as select brainstem nuclei (i.e., substantia nigra, oculomotor nucleus, reticulotegmental nucleus of the pons, facial, lateral vestibular, and raphe interpositus nuclei, inferior olive). All of these degenerated brain gray matter structures are known as consistent targets of the underlying pathological process in heterozygous SCA2 patients. Since they were already involved in our patient within 3 years after disease onset, we think that we were for the first time able to identify the early brain targets of the pathological process of SCA2.

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Acknowledgments

Supported by grants from the Deutsche Forschungsgemeinschaft (RU 1215/1-2), the ADCA-Vereniging Nederland, and the Bernd Fink-Stiftung (Düsseldorf, Germany). BM was founded by the following grants: OTKA 73430 ETT 243/2009 and EUROSCA LSHM-CT-2004-503304. The skillful assistance of M. Babl (tissue processing and immunohistochemistry), I. Szasz (graphics), and M. Hütten (secretary) is thankfully acknowledged. We want to thank W.P. Gai for the donation of the alpha-synuclein antibody.

Conflict of Interest

All authors have no actual or potential conflicts of interest to disclose, including financial, personal, or other relationships with other people or organizations.

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Authors and Affiliations

  1. Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe-University, 60590, Frankfurt am Main, Germany

    Franziska Hoche, Thomas Deller & Udo Rüb

  2. Department of Neurology and Stroke, County Hospital, Veszprém, Hungary

    Laszlo Balikó, Katalin Steinecker & Laszlo Bartos

  3. Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, 5970 RB, Groningen, The Netherlands

    Wilfred den Dunnen

  4. Department of Medical Genetics, University of Pécs, Pécs, Hungary

    Eniko Sáfrány & Bela Melegh

  5. Department of Neurology, Molecular Neurogenetics, Goethe-University, 60590, Frankfurt am Main, Germany

    Georg Auburger

  6. Dr. Senckenberg Chronomedical Institute, Goethe-University, 60590, Frankfurt am Main, Germany

    Horst-Werner Korf

  7. Department of Neurology, University Hospital of Bonn, 53105, Bonn, Germany

    Thomas Klockgether

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  1. Franziska Hoche
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  2. Laszlo Balikó
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Correspondence to Udo Rüb.

Additional information

Franziska Hoche and Laszlo Balikó are joint first authors.

Udo Rüb and Bela Melegh are joint senior authors.

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Hoche, F., Balikó, L., den Dunnen, W. et al. Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage. Cerebellum 10, 245–253 (2011). https://doi.org/10.1007/s12311-010-0239-9

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