A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome

Am J Hum Genet. 1992 Aug;51(2):299-306.


A gene designated "FMR-1" has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involved in the clinical manifestation of the fragile-X syndrome and also in the expression of the cellular phenotype. A deletion including the HTF island and exons of the FMR-1 gene was detected in a fragile X-negative mentally retarded male who presented the clinical phenotype of the fragile-X syndrome. The deletion involves less than 250 kb of genomic DNA, including DXS548 and at least five exons of the FMR-1 gene. These data support the hypothesis that loss of function of the FMR-1 gene leads to the clinical phenotype of the fragile-X syndrome. In the fragile-X syndrome, there are pathogenetic mechanisms other than amplification of the CGG repeat that do have the same phenotypic consequences.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child
  • Chromosome Deletion*
  • DNA
  • DNA Probes
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nucleic Acid Hybridization
  • Phenotype
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA-Binding Proteins*
  • Restriction Mapping


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