CGG repeat in the FMR1 gene: size matters

• Published in: Clinical genetics Vol. 80; no. 3; pp. 214 - 225
• Main Authors: Willemsen, R, Levenga, J, Oostra, BA
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2011; Wiley-Blackwell
• Subjects: 5' Untranslated Regions; Aged; Animals; Ataxia; Ataxia - complications; Ataxia - drug therapy; Ataxia - genetics; Ataxia - physiopathology; Biological and medical sciences; Brain - metabolism; Brain - pathology; CGG repeat; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Disease Models, Animal; DNA Methylation; Female; FMR1; fragile X mental retardation protein; Fragile X Mental Retardation Protein - genetics; Fragile X Mental Retardation Protein - metabolism; Fragile X syndrome; Fragile X Syndrome - complications; Fragile X Syndrome - drug therapy; Fragile X Syndrome - genetics; Fragile X Syndrome - physiopathology; Fundamental and applied biological sciences. Psychology; FXPOI; FXTAS; Gene Expression; General aspects. Genetic counseling; Genetic Association Studies; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Geriatrics; Humans; Medical genetics; Medical sciences; Mental retardation; Mice; Mice, Knockout; Molecular and cellular biology; Mutation; Neurodegenerative diseases; Neurons - metabolism; Neurons - pathology; Neurotransmission; Pathogenesis; Phenotype; Prescription Drugs - administration & dosage; Prescription Drugs - therapeutic use; Primary Ovarian Insufficiency - complications; Primary Ovarian Insufficiency - drug therapy; Primary Ovarian Insufficiency - genetics; Primary Ovarian Insufficiency - physiopathology; Promoters; Reviews; RNA; treatment; tremor; Trinucleotide Repeats - genetics; Human; Chromosome fragility; CGG repeat; Repeated sequence; Size; FMR1; Developmental disorder; Mental retardation; Treatment; FXTAS; Intellectual deficiency; Genetics; Fragile X syndrome; FXPOI
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2011.01723.x

Willemsen R, Levenga J, Oostra BA. CGG repeat in the FMR1 gene: size matters. 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.