title: CGG repeat in the FMR1 gene: size matters.
abstract: The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs (full mutation: FM) generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The absence of FMR1 protein, FMRP, seen in FM is the cause of the mental retardation in patients with FXS. The premutation (PM) is defined as 55-200 CGGs. Female PM carriers are at risk of developing primary ovarian insufficiency. Elderly PM carriers might develop a progressive neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome (FXTAS). Although arising from the mutations in the same gene, distinct mechanisms lead to FXS (absence of FMRP), FXTAS (toxic RNA gain-of-function) and FXPOI. The pathogenic mechanisms thought to underlie these disorders are discussed. This review gives insight on the implications of all possible repeat length categories seen in fragile X families.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Willemsen
authors.forename: J
authors.initials: J
authors.lastname: Levenga
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
mesh_terms: D020121:5' Untranslated Regions; D000368:Aged; D000818:Animals; D001259:Ataxia / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D015870:Gene Expression; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D055553:Prescription Drugs / Q000008:administration & dosage / Q000627:therapeutic use; D016649:Primary Ovarian Insufficiency / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D051860:Fragile X Messenger Ribonucleoprotein 1; D055553:Prescription Drugs; C497683:FMR1 protein, human