Molecular pathogenesis of fragile X-associated tremor/ataxia syndrome

Christopher Raske, Paul J Hagerman

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Fragile X-associated tremor/ataxia syndrome is a late adult onset neurodegenerative disorder that affects individuals who carry a premutation CGG repeat expansion (55-200 CGG repeats) in the 5′ untranslated portion of the fragile X mental retardation 1 (FMR1) gene. Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the CGG expansion. Overexpression of the expanded CGG repeat messenger RNA results in a direct gain-of-function cellular toxicity that is believed to form the pathogenic basis for fragile X-associated tremor/ataxia syndrome. This mechanism is entirely different from the mechanism giving rise to fragile X syndrome, which is due to transcriptional silencing and consequent loss of FMR1 protein. Much of the research in the field has focused on understanding the link between the pathogenic FMR1 messenger RNA and the potential proteins that interact with it.

Original languageEnglish (US)
Pages (from-to)825-829
Number of pages5
JournalJournal of Investigative Medicine
Volume57
Issue number8
DOIs
StatePublished - Dec 2009

Keywords

  • Autism
  • CGG
  • Fragile X
  • Neurodegeneration
  • Neuropathy
  • Trinucleotide

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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