ABSTRACT
This chapter summarizes the molecular studies of the FRAXE and FRAXF fragile sites and discusses the evidence for a clinical phenotype associated with their expression. The gene associated with the FRAXE fragile site and CpG island has been identified and termed FMR2. FRAXF is the third fragile site in the Xq27–q28 region of the human X chromosome, distal to FRAXE by more than 700 kb. This folate-sensitive fragile site is indistinguishable from FRAXA and FRAXE by conventional cytogenetic analysis. In the light of the learning difficulties and mild mental retardation found in FRAXE patients, the higher levels of expression in these particular brain tissues may provide valuable clues as to the role of this gene. Most FRAXE and FRAXF subjects have been identified from mentally impaired individuals referred for fragile X screening, who express a fragile site at Xq27–q28 but who do not have a trinucleotide repeat expansion at the FRAXA site.
