Sjl. Knight et al., TRINUCLEOTIDE REPEAT AMPLIFICATION AND HYPERMETHYLATION OF A CPG ISLAND IN FRAXE MENTAL-RETARDATION, Cell, 74(1), 1993, pp. 127-134
We have cloned the fragile site FRAXE and demonstrate that individuals
with this fragile site possess amplifications of a GCC repeat adjacen
t to a CpG island in Xq28 of the human X chromosome. Normal individual
s have 6-25 copies of the GCC repeat, whereas mentally retarded, FRAXE
-positive individuals have >200 copies and also have methylation at th
e CpG island. This situation is similar to that seen at the FRAXA locu
s 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 unst
able when passed through the male or female line. These results also h
ave implications for the understanding of chromosome fragility.