Fragile X syndrome results from mutations in a (CGG). repeat found in the coding sequence of the FM+ 1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are melotlcally unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expanslon during oogenesis to the full mutation associated with mental retardatlon increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.