Triplet RepeatExpansion attheFRAXELocusandX-linked Mild MentalHandicap

Summary We haverecently shownthattheexpression ofthe FRAXEfragile site inXq28isassociated withtheexpansion ofaGCCtrinucleotide repeat. Inthefamilies studied, FRAXEexpression isalso associated withmildmental handicap. Herewepresent dataonfamilies thatpreviously hadbeendiagnosed ashaving thefragile X syndromebutthat later werefound tobenegative fortrinucleotide repeat expansion attheFRAXAlocus. Inthese families wedemonstrate thepresence ofaGCCtrinucleotide repeat expansion attheFRAXElocus. Studies ofthe FRAXElocus ofnormal individuals showthat they have 6-25copies oftherepeat, whereas affected individuals have>200copies. Asinthefragile Xsyndrome, theamplified CpGresidues aremethylated inaffected males.