Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation

Abstract We have cloned the fragile site FRAXE and demonstrate that individuals with this fragile site possess amplifications of a GCC repeat adjacent to a CpG Island in Xq28 of the human X chromosome. Normal individuals have 6–25 copies of the GCC repeat, whereas mentally retarded, FRAXE -positive individuals have >200 copies and also have methylation at the CpG island. This situation is similar to that seen at the FRAXA locus and is another example in which a trinucleotide repeat expansion is associated with a human genetic disorder. In contrast with the fragile X syndrome, the GCC repeat can expand or contract and is equally unstable when passed through the male or female line. These results also have implications for the understanding of chromosome fragility.