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The Pathology of FXTAS

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FXTAS, FXPOI, and Other Premutation Disorders

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Abstract

In 2002, a syndrome of tremor, ataxia, cognitive decline, and the presence of unique ubiquitin staining intranuclear inclusions in the brain was discovered in premutation males carrying an expansion of between 55 and 200 CGG trinucleotide repeats on the FMR1 gene. This clinical syndrome is now known as fragile X-associated tremor/ataxia (FXTAS) and has been found in both male and female carriers of the expanded premutation allele. The goal of this chapter is to summarize what is known about the anatomical pathology associated with the fragile X premutation and particularly in those individuals with FXTAS. Neuropathology in FXTAS was initially found in the central nervous system, but recent evidence has demonstrated pathological features, including intranuclear inclusions, in the peripheral nervous system, the enteric nervous system, and the neuroendocrine system. The precise cellular dysfunctions that underlie these pathologic features are currently under intense investigation with the goal of prevention and treatment of this devastating disorder.

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Abbreviations

DRPLA:

Dentatorubropallidoluysian atrophy

SBMA:

X-linked spinobulbar muscular atrophy (Kennedy’s disease)

NIID:

Neuronal intranuclear inclusion disease

SCA:

Spinocerebellar ataxia

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

5′ UTR:

5′ untranslated region

MS:

Multiple sclerosis

FXTAS:

Fragile X-associated tremor/ataxia syndrome

FMR1 :

Fragile X mental retardation gene

FMRP:

Fragile X mental retardation protein

H&E:

Hematoxylin and eosin stain

HD:

Huntington’s disease

PAS:

Periodic acid-Schiff stain

LFB:

Luxol fast blue stain

MCP:

Middle cerebellar peduncle

IF:

Intermediate filament

NF:

Neurofilament

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Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA, USA

    Veronica Martinez Cerdeno & Claudia Greco

  2. Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, Sacramento, CA, USA

    Veronica Martinez Cerdeno & Claudia Greco

  3. MIND Institute, UC Davis Medical Center, Sacramento, CA, USA

    Veronica Martinez Cerdeno & Claudia Greco

Authors
  1. Veronica Martinez Cerdeno
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  2. Claudia Greco
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Corresponding author

Correspondence to Veronica Martinez Cerdeno .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, University of California, Davis, California, USA

    Flora Tassone

  2. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA

    Deborah A. Hall

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Cerdeno, V.M., Greco, C. (2016). The Pathology of FXTAS. In: Tassone, F., Hall, D. (eds) FXTAS, FXPOI, and Other Premutation Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-33898-9_5

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