Characterization and localization of the FMR-1 gene product associated with fragile X syndrome

Nature. 1993 Jun 24;363(6431):722-4. doi: 10.1038/363722a0.


The fragile X syndrome is the most frequent form of inherited mental retardation after Down's syndrome, having an incidence of one in 1,250 males. The fragile X syndrome results from amplification of the CGG repeat found in the FMR-1 gene. This CGG repeat shows length variation in normal individuals and is increased significantly in both carriers and patients; it is located 250 base pairs distal to a CpG island which is hypermethylated in fragile X patients. The methylation probably results in downregulation of FMR-1 gene expression. No information can be deduced about the function of the FMR-1 protein from its predicted sequence. Here we investigate the nature and function of the protein encoded by the FMR-1 gene using polyclonal antibodies raised against the predicted amino-acid sequences. Four different protein products, possibly resulting from alternative splicing, have been identified by immunoblotting in lymphoblastoid cell lines of healthy individuals. All these proteins were missing in cell lines from patients not expressing FMR-1 messenger RNA. The intracellular localization of the FMR-1 gene products was investigated by transient expression in COS-1 cells and found to be cytoplasmic. Localization was also predominantly cytoplasmic in the epithelium of the oesophagus, but in some cells was obviously nuclear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • DNA, Single-Stranded
  • Escherichia coli
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Molecular Sequence Data
  • Mosaicism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Precipitin Tests
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins*
  • Repetitive Sequences, Nucleic Acid
  • Transfection


  • DNA, Single-Stranded
  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein