The fragile X-associated tremor ataxia syndrome

Research output: Chapter in Book/Report/Conference proceedingChapter

22 Citations (Scopus)

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder clinically characterized by intention tremor and gait ataxia, in addition to other conditions including hypothyroidism, autonomic dysfunction, hypertension, peripheral neuropathy, and cognitive decline. FXTAS affects some males (approximately 40%) and in less degree female premutation carriers (8-16%) older than 50 years with an age-dependent symptomatology and penetrance. The CGG repeat number appears to influence the severity and the age of onset of the disorder. The neuropathological hallmark of FXTAS is the presence of eosinophillic, ubiquitin-positive intranuclear inclusions in both neurons and astroglia throughout brain. FXTAS is due to RNA toxicity caused by elevated levels of CGG-expanded mRNA containing 55-200 CGG repeats, which is found in the intranuclear inclusions that sequester various proteins including ubiquitin, αB-crystallin, lamin A/C, hnRNP A2, myelin basic protein, and Sam68. The expression of the expanded CGG repeat FMR1 mRNA also induces a cellular stress response and leads to a disruption of the nuclear lamin A/C architecture. These alterations are observable even in early development, suggesting that the expanded-repeat mRNA triggers pathogenic mechanisms that can provide a molecular basis for the neurodevelopmental abnormalities observed in some children who are carriers of an FMR1 premutation allele. Finally, the presence of cellular dysregulation in older adults who do not present clinical features of FXTAS may suggest that additional genetic or environmental protective factors may play a role in the pathogenesis of FXTAS.

Original languageEnglish (US)
Title of host publicationResults and Problems in Cell Differentiation
Pages337-357
Number of pages21
Volume54
DOIs
StatePublished - 2012

Publication series

NameResults and Problems in Cell Differentiation
Volume54
ISSN (Print)00801844
ISSN (Electronic)18610412

Fingerprint

Lamin Type A
Intranuclear Inclusion Bodies
Ubiquitin
Messenger RNA
Gait Ataxia
Crystallins
Myelin Basic Protein
Penetrance
Peripheral Nervous System Diseases
Tremor
Hypothyroidism
Age of Onset
Astrocytes
Neurodegenerative Diseases
Fragile X Tremor Ataxia Syndrome
Alleles
RNA
Hypertension
Neurons
Brain

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Tassone, F., & Hagerman, R. J. (2012). The fragile X-associated tremor ataxia syndrome. In Results and Problems in Cell Differentiation (Vol. 54, pp. 337-357). (Results and Problems in Cell Differentiation; Vol. 54). https://doi.org/10.1007/978-3-642-21649-7_18

The fragile X-associated tremor ataxia syndrome. / Tassone, Flora; Hagerman, Randi J.

Results and Problems in Cell Differentiation. Vol. 54 2012. p. 337-357 (Results and Problems in Cell Differentiation; Vol. 54).

Research output: Chapter in Book/Report/Conference proceedingChapter

Tassone, F & Hagerman, RJ 2012, The fragile X-associated tremor ataxia syndrome. in Results and Problems in Cell Differentiation. vol. 54, Results and Problems in Cell Differentiation, vol. 54, pp. 337-357. https://doi.org/10.1007/978-3-642-21649-7_18
Tassone F, Hagerman RJ. The fragile X-associated tremor ataxia syndrome. In Results and Problems in Cell Differentiation. Vol. 54. 2012. p. 337-357. (Results and Problems in Cell Differentiation). https://doi.org/10.1007/978-3-642-21649-7_18
Tassone, Flora ; Hagerman, Randi J. / The fragile X-associated tremor ataxia syndrome. Results and Problems in Cell Differentiation. Vol. 54 2012. pp. 337-357 (Results and Problems in Cell Differentiation).
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