Rare fragile sites

Abstract

Rare folate-sensitive fragile sites are the archetypal trinucleotide repeats. Although the CAG repeat in the androgen receptor, associated with spinobulbar muscular atrophy, was the first to be published in 1991, it was the publication in the same year of the molecular basis of fragile X that focused much attention on trinucleotide repeat expansion as a mutational mechanism. A number of rare fragile sites have had their repeat elements characterised since that time. The so-called "folate-sensitive" fragile sites are likely to be all CCG repeat expansions similar to the fragile X. The folate insensitive fragile sites have more complex longer repeat elements. Only two rare fragile sites (FRAXA and FRAXE) are of unequivocal clinical significance in that they are associated with intellectual disability.