Mosaicism for a full mutation, premutation, and deletion of the CGG repeats results in 22% FMRP and elevated FMR1 mRNA levels in a high-functioning fragile X male

Am J Med Genet A. 2006 Jul 1;140(13):1463-71. doi: 10.1002/ajmg.a.31291.


The molecular basis in the majority of fragile X patients results from expansion of the CGG repeats in the FMR1 gene causing its transcriptional silencing and deficiency of its encoded protein FMRP. In this communication, we report on a male patient who lacks the characteristic physical features of fragile X and carries a fully methylated mutation, a premutation, a non-methylated full mutation, and a microdeletion encompassing the entire CGG repeat region and 42 bp of upstream flanking sequence. Southern blot analysis revealed that the methylated full mutation accounted for only 10% of his genotype while the premutation/non-methylated full mutation and the microdeletion constituted 37% and 53%, respectively. Immunofluorescent staining of FMRP demonstrated the presence of 22% FMRP in his peripheral blood leukocytes and quantitative RT-PCR revealed a 3.6-fold elevation of FMR1 mRNA levels. Developmental assessments indicated that while he has a learning disability, he does not have mental retardation. Because previous reports had noted that 28% FMRP expression is associated with a characteristic fragile X phenotype, we propose that in our patient the association of 22% FMRP levels with normal physical features and a high-functioning status may have resulted from increased FMRP stability by a mechanism that takes into account the CGG microdeletion and elevated mRNA levels.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Blotting, Southern
  • Blotting, Western
  • DNA / analysis
  • DNA / chemistry
  • DNA / genetics
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Mental Retardation Protein / metabolism
  • Fragile X Syndrome / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mosaicism*
  • Mutation / genetics*
  • Nucleic Acid Conformation
  • Pedigree
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion / genetics*
  • Trinucleotide Repeat Expansion / genetics*


  • FMR1 protein, human
  • RNA, Messenger
  • Fragile X Mental Retardation Protein
  • DNA