The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm

Nat Genet. 1993 Jun;4(2):143-6. doi: 10.1038/ng0693-143.


Fragile X syndrome is characterized at the molecular level by amplification of a (CGG)n repeat and hypermethylation of a CpG island preceeding the open reading frame of the fragile X gene (FMR-1) located in Xq27.3. Anticipation in this syndrome is associated with progressive amplification of the (CGG)n repeat from a premutation to a full mutation through consecutive generations. Remarkably, expansion of the premutation to the full mutation is strictly maternal. To clarify this parental influence we studied FMR-1 in sperm of four male fragile X patients. This showed that only the premutation was present in their sperm, although they had a full mutation in peripheral lymphocytes. This might suggest that expansion of the premutation to the full mutation in FMR-1 does not occur in meiosis but in a postzygotic stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • Embryonic and Fetal Development / genetics
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Gene Amplification*
  • Humans
  • Lymphocytes / chemistry
  • Male
  • Meiosis
  • Methylation
  • Models, Genetic*
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Open Reading Frames
  • Polymerase Chain Reaction
  • RNA-Binding Proteins*
  • Repetitive Sequences, Nucleic Acid*
  • Sex Characteristics
  • Spermatozoa / chemistry*


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