title: Identification of the gene FMR2, associated with FRAXE mental retardation.
abstract: Five folate-sensitive fragile sites have been characterized at the molecular level (FRAXA, FRAXE, FRAXF, FRA16A and FRA11B). Three of them (FRAXA, FRAXE and FRA11B) are associated with clinical problems, and two of the genes (FMR1 in FRAXA and CBL2 in FRA11B) have been identified. All of these fragile sites are associated with (CCG)n/(CGG)n triplet expansions which are hypermethylated beyond a critical size. FRAXE is a rare folate sensitive fragile site only recently recognized. Its cytogenetic expression was found to involve the amplification of a (CCG)n repeat adjacent to a CpG island. Normal alleles vary from 6 to 25 copies. Expansions of greater than 200 copies were found in FRAXE expressing males and their FRAXE associated CpG island was fully methylated. An association of FRAXE expression with concurrent methylation of the CpG island and mild non-specific mental handicap in males has been reported by several groups. We now report the cloning and characterization of a gene (FMR2) adjacent to FRAXE. Elements of FMR2 were initially identified from sequences deleted from a developmentally delayed boy. We correlate loss of FMR2 expression with (CCG)n expansion at FRAXE, demonstrating that this is a gene associated with the CpG island adjacent to FRAXE and contributes for FRAXE-associated mild mental retardation.
authors.affiliation: Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Gecz
authors.forename: A K
authors.initials: AK
authors.lastname: Gedeon
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002648:Child; D018244:Chromosomes, Artificial, Yeast; D017931:DNA Primers; D015342:DNA Probes; D015226:Dinucleoside Phosphates; D005091:Exons; D005260:Female; D005333:Fetus; D005600:Fragile X Syndrome / Q000235:genetics*; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators
chemical_list: D017931:DNA Primers; D015342:DNA Probes; D015226:Dinucleoside Phosphates; D009687:Nuclear Proteins; D011506:Proteins; D015534:Trans-Activators; C099930:AFF2 protein, human; C015772:CpG dinucleotide