Fragile X-associated tremor/ataxia syndrome

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some but not all carriers of small, noncoding CGG-repeat expansions (55-200 repeats; premutation) within the fragile X gene (FMR1). Principal features of FXTAS include intention tremor, cerebellar ataxia, Parkinsonism, memory and executive function deficits, autonomic dysfunction, brain atrophy with white matter disease, and cognitive decline. Although FXTAS was originally considered to be confined to the premutation range, rare individuals with a gray zone (45-54 repeats) or an unmethylated full mutation (>200 repeats) allele have now been described, the constant feature of the disorder remaining the requirement for FMR1 expression, in contradistinction to the gene silencing mechanism of fragile X syndrome. Although transcriptional activity is required for FXTAS pathogenesis, the specific trigger(s) for FXTAS pathogenesis remains elusive, highlighting the need for more research in this area. This need is underscored by recent neuroimaging findings of changes in the central nervous system that consistently appear well before the onset of clinical symptoms, thus creating an opportunity to delay or prevent the appearance of FXTAS.

Original languageEnglish (US)
Pages (from-to)58-70
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1338
Issue number1
DOIs
StatePublished - Mar 1 2015

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Genes
Neuroimaging
Neurology
Brain
Data storage equipment
Leukoencephalopathies
Fragile X Syndrome
Cerebellar Ataxia
Executive Function
Parkinsonian Disorders
Gene Silencing
Tremor
Neurodegenerative Diseases
Atrophy
Fragile X Tremor Ataxia Syndrome
Syndrome
Central Nervous System
Alleles
Mutation
Repeats

Keywords

  • CGG repeat
  • Dementia
  • FXTAS
  • Neurodegeneration
  • Premutation
  • RNA toxicity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Fragile X-associated tremor/ataxia syndrome. / Hagerman, Paul J; Hagerman, Randi J.

In: Annals of the New York Academy of Sciences, Vol. 1338, No. 1, 01.03.2015, p. 58-70.

Research output: Contribution to journalArticle

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