Understanding the molecular basis of fragile X syndrome

• Published in: Human molecular genetics Vol. 9; no. 6; pp. 901 - 908
• Main Authors: PENG JIN, WARREN, S. T
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 12.04.2000; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); DNA Methylation; FMR1 gene; FMR1 protein; fragile X syndrome; Fragile X Syndrome - genetics; Humans; Medical genetics; Medical sciences; Trinucleotide Repeats; Human; Chromosome fragility; Cell function; Pathogenesis; Microsatellite DNA; RNA binding protein; Review; Repression; Fragile X syndrome; Gene expression; Methylation
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/9.6.901

Fragile X syndrome, a common form of inherited mental retardation, is mainly caused by massive expansion of CGG triplet repeats located in the 5'-untranslated region of the fragile X mental retardation-1 ( FMR1 ) gene. In patients with fragile X syndrome, the expanded CGG triplet repeats are hypermethylated and the expression of the FMR1 gene is repressed, which leads to the absence of FMR1 protein (FMRP) and subsequent mental retardation. FMRP is an RNA-binding protein that shuttles between the nucleus and cytoplasm. This protein has been implicated in protein translation as it is found associated with polyribosomes and the rough endoplasmic reticulum. We discuss here the recent progress made towards understanding the molecular mechanism of CGG repeat expansion and physiological function(s) of FMRP. These studies will not only help to illuminate the molecular basis of the general class of human diseases with trinucleotide repeat expansion but also provide an avenue to understand aspects of human cognition and intelligence.