Length of uninterrupted CGG repeats determines instability in the FMR1 gene

Nat Genet. 1994 Sep;8(1):88-94. doi: 10.1038/ng0994-88.


Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides within the CGG repeat tract of the FMR1 gene revealed that most alleles possess two interspersed AGGs and that the longest tract of uninterrupted CGG repeats is usually found at the 3' end. Variation in the length of the repeat appears polar. Alleles containing between 34 and 55 repeats, with documented unstable transmissions, were shown to have lost one or both AGG interruptions. These comparisons define an instability threshold of 34-38 uninterrupted CGG repeats. Analysis of premutation alleles in Fragile X syndrome carriers reveals that 70% of these alleles contain a single AGG interruption. These data suggest that the loss of an AGG is an important mutational event in the generation of unstable alleles predisposed to the Fragile X syndrome.

Publication types

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

MeSH terms

  • Base Sequence
  • DNA
  • Fragile X Mental Retardation Protein
  • Humans
  • Male
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • RNA-Binding Proteins*
  • Repetitive Sequences, Nucleic Acid
  • X Chromosome*


  • FMR1 protein, human
  • Nerve Tissue Proteins
  • Okazaki fragments
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein
  • DNA

Associated data

  • GENBANK/S74494