title: Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation.
abstract: We have cloned the fragile site FRAXE and demonstrate that individuals with this fragile site possess amplifications of a GCC repeat adjacent to a CpG island in Xq28 of the human X chromosome. Normal individuals have 6-25 copies of the GCC repeat, whereas mentally retarded, FRAXE-positive individuals have > 200 copies and also have methylation at the CpG island. This situation is similar to that seen at the FRAXA locus 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 unstable when passed through the male or female line. These results also have implications for the understanding of chromosome fragility.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, England.
authors.forename: S J
authors.initials: SJ
authors.lastname: Knight
authors.forename: A V
authors.initials: AV
authors.lastname: Flannery
authors.forename: M C
authors.initials: MC
authors.lastname: Hirst
authors.forename: L
authors.initials: L
authors.lastname: Campbell
authors.forename: Z
authors.initials: Z
authors.lastname: Christodoulou
authors.forename: S R
authors.initials: SR
authors.lastname: Phelps
authors.forename: J
authors.initials: J
authors.lastname: Pointon
authors.forename: H R
authors.initials: HR
authors.lastname: Middleton-Price
authors.forename: A
authors.initials: A
authors.lastname: Barnicoat
authors.forename: M E
authors.initials: ME
authors.lastname: Pembrey
mesh_terms: D001483:Base Sequence; D005600:Fragile X Syndrome / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome