title: FMR2 expression in families with FRAXE mental retardation.
abstract: Normal individuals express the two alternative transcripts, FMR2 and Ox19, from the FRAXE-associated CpG island. Molecular analysis of the Ox19 transcript suggests that it is a truncated isoform of the FMR2 gene with an alternative 3' end. Both isoforms showed a similar pattern of expression, with the Ox19 isoform expressed at a much lower level. Fibroblasts, chorionic villi and hair roots showed the highest level of FMR2 expression, whole blood cells and amniocytes showed very low expression, and the transcript was not detected in lymphoblasts. Fibroblasts of 11 individuals from seven families segregating FRAXE were assayed for FMR2 expression and FRAXE CpG island methylation. A man with an unmethylated expansion of 0.6 kb expressed FMR2 and represents a pre-mutation carrier. All chromosomes with FRAXE CCG expansions of 0.8 kb or greater were fully methylated and did not express the FMR2 gene, analogous to the mechanism of silencing the FMR1 gene in carriers of the FRAXA full mutation. The boundary between FRAXE pre-mutation and FRAXE full mutation is between 0.7 and 0.8 kb. Two men with absence of FMR2 expression in fibroblasts were not mentally impaired, suggesting that IQ in some men with FRAXE full mutation may remain within the normal range. Although molecular tools to study FRAXE non-specific mental retardation are now available, further psychometric and molecular studies are needed to characterize the effect of the FRAXE full mutation for the purpose of genetic counselling.
authors.affiliation: Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Gécz
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: A
authors.initials: A
authors.lastname: Hockey
authors.forename: P
authors.initials: P
authors.lastname: Carbonell
authors.forename: G
authors.initials: G
authors.lastname: Turner
authors.forename: E A
authors.initials: EA
authors.lastname: Haan
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D004303:Dosage Compensation, Genetic; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005453:Fluorescence; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D015870:Gene Expression; D006580:Genetic Carrier Screening; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D017421:Sequence Analysis; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators
chemical_list: D017931:DNA Primers; D051860:Fragile X Messenger Ribonucleoprotein 1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C099930:AFF2 protein, human; C497683:FMR1 protein, human