Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat

Nat Genet. 1993 Jul;4(3):244-51. doi: 10.1038/ng0793-244.


Fragile X syndrome is associated with massive expansion of a CGG trinucleotide repeat within the FMR-1 gene and transcriptional silencing of the gene due to abnormal methylation. Partial cDNA sequence of the human FMR-1 has been reported. We report here the isolation and characterization of cDNA clones encoding the murine homologue, fmr-1, which exhibit marked sequence identity with the human gene, including the conservation of the CGG repeat. A conserved ATG downstream of the CGG repeat in human and mouse and an in-frame stop codon in other human 5' cDNA sequences demarcate the FMR-1 coding region and confine the CGG repeat to the 5' untranslated region. We also present evidence for alternative splicing of the FMR-1 gene in mouse and human brain and show that one of these splicing events alters the FMR-1 reading frame, predicting isoforms with novel carboxy termini.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Female
  • Fragile X Syndrome / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / genetics
  • Protein Biosynthesis
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Species Specificity


  • Oligodeoxyribonucleotides