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Acta Neuropathologica
Erschienen in: Acta Neuropathologica 4/2011

01.10.2011 | Original Paper

Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice

verfasst von: Michael R. Hunsaker, Claudia M. Greco, Marian A. Spath, Arie P. T. Smits, Celestine S. Navarro, Flora Tassone, Johan M. Kros, Lies-Anne Severijnen, Elizabeth M. Berry-Kravis, Robert F. Berman, Paul J. Hagerman, Rob Willemsen, Randi J. Hagerman, Renate K. Hukema

Erschienen in: Acta Neuropathologica | Ausgabe 4/2011

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Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder generally presenting with intention tremor and gait ataxia, but with a growing list of co-morbid medical conditions including hypothyroidism, hypertension, peripheral neuropathy, and cognitive decline. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in both neurons and astroglia. However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS). To address this issue, we surveyed non-CNS organs in ten human cases with FXTAS and in a CGG repeat knock-in (CGG KI) mouse model known to possess neuronal and astroglial inclusions. We find inclusions in multiple tissues from FXTAS cases and CGG KI mice, including pancreas, thyroid, adrenal gland, gastrointestinal, pituitary gland, pineal gland, heart, and mitral valve, as well as throughout the associated autonomic ganglia. Inclusions were observed in the testes, epididymis, and kidney of FXTAS cases, but were not observed in mice. These observations demonstrate extensive involvement of the peripheral nervous system and systemic organs. The finding of intranuclear inclusions in non-CNS somatic organ systems, throughout the PNS, and in the enteric nervous system of both FXTAS cases as well as CGG KI mice suggests that these tissues may serve as potential sites to evaluate early intervention strategies or be used as diagnostic factors.
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Metadaten
Titel
Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice
verfasst von
Michael R. Hunsaker
Claudia M. Greco
Marian A. Spath
Arie P. T. Smits
Celestine S. Navarro
Flora Tassone
Johan M. Kros
Lies-Anne Severijnen
Elizabeth M. Berry-Kravis
Robert F. Berman
Paul J. Hagerman
Rob Willemsen
Randi J. Hagerman
Renate K. Hukema
Publikationsdatum
01.10.2011
Verlag
Springer-Verlag
Erschienen in
Acta Neuropathologica / Ausgabe 4/2011
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-011-0860-9

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