TRIPLET REPEAT EXPANSION AT THE FRAXE LOCUS AND X-LINKED MILD MENTAL HANDICAP

We have recently shown that the expression of the FRAXE fragile site i n Xq28 is associated with the expansion of a GCC trinucleotide repeat. In the families studied, FRAXE expression is also associated with mil d mental handicap. Here we present data on families that previously ha d been diagnosed as having the fragile X syndrome but that later were found to be negative for trinucleotide repeat expansion at the FRAXA l ocus. In these families we demonstrate the presence of a GCC trinucleo tide repeat expansion at the FRAXE locus. Studies of the FRAXE locus o f normal individuals show that they have 6-25 copies of the repeat, wh ereas affected individuals have >200 copies. As in the fragile X syndr ome, the amplified CpG residues are methylated in affected males.