New perspectives on the biology of fragile X syndrome

Curr Opin Genet Dev. 2012 Jun;22(3):256-63. doi: 10.1016/j.gde.2012.02.002. Epub 2012 Feb 28.


Fragile X syndrome (FXS) is a trinucleotide repeat disorder caused by a CGG repeat expansion in FMR1, and loss of its protein product FMRP. Recent studies have provided increased support for the role of FMRP in translational repression via ribosomal stalling and the microRNA pathway. In neurons, particular focus has been placed on identifying the signaling pathways such as PI3K and mTOR downstream of group 1 metabotropic glutamate receptors (mGluR1/5) that regulate FMRP. New evidence also suggests that loss of FMRP causes presynaptic dysfunction and abnormal adult neurogenesis. In addition, studies on FXS stem cells especially induced pluripotent stem (iPS) cells and new sequencing efforts hold out promise for deeper understanding of the silencing process and mutation spectrum of FMR1.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alleles
  • Electrical Synapses / genetics
  • Electrical Synapses / metabolism
  • Epigenesis, Genetic
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Mental Retardation Protein / metabolism
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • MAP Kinase Signaling System
  • Mutation, Missense
  • Neurogenesis
  • Neurons / metabolism
  • Neurons / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Biosynthesis
  • RNA Interference
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism


  • FMR1 protein, human
  • Receptors, Metabotropic Glutamate
  • Fragile X Mental Retardation Protein
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases