Acta Neuropathologica

, 122:467 | Cite as

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

  • 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
Original Paper


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.


FXTAS Intranuclear inclusions Fragile X premutation CGG KI mouse 


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Michael R. Hunsaker
    • 1
  • Claudia M. Greco
    • 2
    • 3
  • Marian A. Spath
    • 4
  • Arie P. T. Smits
    • 4
  • Celestine S. Navarro
    • 2
  • Flora Tassone
    • 5
    • 6
  • Johan M. Kros
    • 7
  • Lies-Anne Severijnen
    • 8
  • Elizabeth M. Berry-Kravis
    • 9
  • Robert F. Berman
    • 1
    • 3
    • 6
  • Paul J. Hagerman
    • 3
    • 5
    • 6
  • Rob Willemsen
    • 6
    • 8
  • Randi J. Hagerman
    • 3
    • 6
    • 10
  • Renate K. Hukema
    • 8
  1. 1.Department of Neurological SurgeryUniversity of California, DavisDavisUSA
  2. 2.Department of PathologyUniversity of California, DavisDavisUSA
  3. 3.M.I.N.D. InstituteUniversity of California at Davis Medical CenterSacramentoUSA
  4. 4.Department of Human GeneticsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  5. 5.Department of Biochemistry and Molecular MedicineUniversity of California, DavisDavisUSA
  6. 6.NeuroTherapeutics Research InstituteUniversity of California, DavisDavisUSA
  7. 7.Department of PathologyErasmus MCRotterdamThe Netherlands
  8. 8.CBG-Department of Clinical GeneticsErasmus MCRotterdamThe Netherlands
  9. 9.Departments of Pediatrics, Neurological Sciences, and BiochemistryRush University Medical CenterChicagoUSA
  10. 10.Department of PediatricsUniversity of California at Davis Medical CenterSacramentoUSA

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