The pathophysiology of fragile x syndrome

Annu Rev Genomics Hum Genet. 2007;8:109-29. doi: 10.1146/annurev.genom.8.080706.092249.


Fragile X syndrome is the most common form of inherited mental retardation. The disorder is mainly caused by the expansion of the trinucleotide sequence CGG located in the 5' UTR of the FMR1 gene on the X chromosome. The abnormal expansion of this triplet leads to hypermethylation and consequent silencing of the FMR1 gene. Thus, the absence of the encoded protein (FMRP) is the basis for the phenotype. FMRP is a selective RNA-binding protein that associates with polyribosomes and acts as a negative regulator of translation. FMRP appears to play an important role in synaptic plasticity by regulating the synthesis of proteins encoded by certain mRNAs localized in the dendrite. An advancing understanding of the pathophysiology of this disorder has led to promising strategies for pharmacologic interventions.

Publication types

  • Review

MeSH terms

  • Base Sequence
  • Chromosomes, Human, X / genetics
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / etiology*
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / therapy
  • Humans
  • Inheritance Patterns / physiology
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / physiology
  • Neurons / physiology
  • Nucleic Acid Conformation
  • Trinucleotide Repeats / genetics


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein