Triplet repeat expansion at the FRAXE locus and X-linked mild mental handicap

• Published in: American journal of human genetics Vol. 55; no. 1; pp. 81 - 86
• Main Authors: KNIGHT, S. J. L, VOELCKEL, M. A, HIRST, M. C, FLANNERY, A. V, MONCLA, A, DAVIES, K. E
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01-07-1994
• Subjects: BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); CHROMOSOMES; DETECTION; Dinucleoside Phosphates - genetics; DNA - genetics; Down Syndrome - complications; ETIOLOGY; Female; Fragile X Syndrome - complications; Fragile X Syndrome - genetics; Fragile X Syndrome - pathology; GENE MUTATIONS; GENETIC MAPPING; HETEROCHROMOSOMES; HUMAN CHROMOSOMES; HUMAN X CHROMOSOME; Humans; Male; MAPPING; Medical genetics; Medical sciences; MENTAL DISORDERS; MUTATIONS; Pedigree; Phenotype; Repetitive Sequences, Nucleic Acid; Restriction Mapping; X CHROMOSOME 550400 > Genetics; Human; Chromosome fragility; Sex linked character; Fragile site; Family study; Repeated sequence; Trinucleotide; Gene expression; Mental retardation; Differential diagnostic; Genetic disease; X-Chromosome; Fragile X syndrome; Methylation
• ISSN: 0002-9297; 1537-6605

We have recently shown that the expression of the FRAXE fragile site in Xq28 is associated with the expansion of a GCC trinucleotide repeat. In the families studied, FRAXE expression is also associated with mild mental handicap. Here we present data on families that previously had been diagnosed as having the fragile X syndrome but that later were found to be negative for trinucleotide repeat expansion at the FRAXA locus. In these families we demonstrate the presence of a GCC trinucleotide repeat expansion at the FRAXE locus. Studies of the FRAXE locus of normal individuals show that they have 6-25 copies of the repeat, whereas affected individuals have > 200 copies. As in the fragile X syndrome, the amplified CpG residues are methylated in affected males.