Fragile X Syndrome

J. T. Gonçalves, C. Portera-Cailliau

Research output: Chapter in Book/Report/Conference proceedingChapter


Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and the best understood single-gene cause of autism. It is most often caused by a trinucleotide repeat expansion in the FMR1 (fragile X mental retardation 1) gene on the X chromosome, first identified in 1991, resulting in the transcriptional repression of the gene. Intellectual disability, autistic traits, abnormal facial features, and macroorchidism are among the most common clinical features in affected individuals. Although the brains of individuals with FXS have few gross anatomical defects, at the cytological level there is an overabundance of immature dendritic spines of neurons in the cerebral cortex. Similar spine defects are reproduced in the Fmr1 knockout mouse model of FXS. In addition to spine dysgenesis, diminished inhibition and excessive metabotropic glutamate receptor signaling in the brain are the most widely studied alterations in the mutant mice. A major area of investigation is the identification of signaling pathways regulated by the fragile X mental retardation protein (FMRP). FMRP is an mRNA-binding protein that represses the translation of key synaptic proteins, presumably by stalling ribosomal translocation on its target RNAs. Through this work, a variety of molecules implicated in the structural and functional synaptic abnormalities in Fmr1 null mice have already been identified as potential therapeutic targets and are now being pursued in several FXS clinical trials.

Original languageEnglish (US)
Title of host publicationBrenner's Encyclopedia of Genetics
Subtitle of host publicationSecond Edition
PublisherElsevier Inc.
Number of pages4
ISBN (Electronic)9780080961569
ISBN (Print)9780123749840
StatePublished - Feb 27 2013
Externally publishedYes


  • Autism
  • Dendritic spine
  • Fragile X mental retardation protein
  • Fragile X syndrome
  • Long-term depression
  • Long-term potentiation
  • Mental impairment
  • Metabotropic glutamate receptor
  • Methylation
  • Plasticity
  • Synapse
  • Trinucleotide repeat

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine


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