Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion

Nat Genet. 1993 Jun;4(2):140-2. doi: 10.1038/ng0693-140.


We demonstrate here that somatic variation of CGG repeat length is based on a mosaic of cells with different but stable FMR-1 alleles and does not reflect permanent mitotic instability. The length of a particular allele in an individual cell was maintained in progeny cells establishing a clone. The mutation patterns of multiple repeats in the DNA of fetal tissues were identical and did not significantly change during proliferation in vitro. It is proposed that genotype mosaicism and expansion to full mutation are generated post-conceptionally by the same molecular mechanism in a particular window of early development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cell Differentiation
  • Cell Division
  • Clone Cells / pathology
  • Embryonic and Fetal Development / genetics*
  • Female
  • Fetus / pathology
  • Fibroblasts / pathology
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / embryology
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / pathology
  • Gene Amplification*
  • Humans
  • Male
  • Mitosis*
  • Mosaicism
  • Nerve Tissue Proteins / genetics*
  • Placenta / pathology
  • RNA-Binding Proteins*
  • Repetitive Sequences, Nucleic Acid*


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