Mosaicism of a microdeletion of 486 bp involving the CGG repeat of the FMR1 gene due to misalignment of GTT tandem repeats at chi-like elements flanking both breakpoints and a full mutation

Hum Genet. 1996 Oct;98(4):409-14. doi: 10.1007/s004390050230.

Abstract

Although the majority of fragile-X patients demonstrate methylation and a much-expanded CGG repeat region in the 5'-untranslated region of exon 1 of the FMR1 gene, exceptional cases have been reported to be due to deletions. However, fine mapping of the deletion breakpoints is still lacking and so far the underlying mechanism is unknown. We identified a fragile-X patient mosaic for a full mutation and a microdeletion. The microdeletion spans 486 bp, involving 168 bp upstream from the CGG repeat region, the entire CGG repeat region, exon 1, and 138 bp of the first intron of the FMR1 gene. In contrast to previous reports, the 5' breakpoint does not fall into the hotspot region. The proximal breakpoint, 5'-GTGGTT/T-3', and the distal breakpoint, 5'-GTTGTT/GG-3', can be characterized as chi-like elements and are flanked by direct tandem repeats. Mosaicism of a full mutation and the microdeletion in the DNA of the patient's leukocytes indicates the mitotic origin of the microdeletion. Since the microdeletion allele is unmethylated, it can be concluded that it is not derived from the methylated full mutation but from an unmethylated premutational allele.

Publication types

  • Case Reports

MeSH terms

  • Base Composition
  • Base Sequence
  • Child, Preschool
  • DNA Replication
  • DNA, Antisense
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Humans
  • Leukocytes
  • Male
  • Models, Genetic
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Polymerase Chain Reaction
  • RNA-Binding Proteins / genetics
  • Sequence Deletion*
  • Trinucleotide Repeats*

Substances

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

Associated data

  • GENBANK/L29074