Fragile X mental retardation

Mazroui, R., Huot, M. E., Tremblay, S., Filion, C., Labelle, Y., and Khandjian, E. W. (2002). Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 11, 3007—3017. 

Zalfa, F. and Bagni, C. Molecular insights into mental retardation multiple functions for the Fragile X mental retardation protein Curr. Issues Mol. Biol. 6 73-88, 2004. 

Fragile X syndrome has some things in common with Hnntington s disease. The genetic defect is in the FMRl (Fragile X mental retardation 1) gene. The affected protein is FMRP (Fragile X mental retardation protein). 

Biacsi, R., Kumari, D. and Usdin, K. (2008) SIRTl inhibition alleviates gene silencing in Fragile X mental retardation syndrome. PLoS Genetics, 4, el000017. 

Figure 1-5. Diagram of the fragile X mental retardation (FAIR ) gene with restriction map and FMR1 probes used for diagnostic Southern blots. The circle indicates the CpG island, and the box represents the first exon. The dark region shows the location of triplet repeats.

Eberhart DE, Malter HE, Feng Y, et al. The fragile X mental retardation protein is a ribonucleopro-tein containing both nuclear localization and nuclear export signals. Hum Mol Genet 5 1083-1091,1996. 

Bear ME, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27 370-377... 

Reeve SP, Bassetto L, Genova GK, Kleyner Y, Leyssen M, Jackson FR, Hassan BA (2005) The Drosophila fragile X mental retardation protein controls actin dynamics by directly regulating profilin in the brain. CurrBiol 15 1156-1163... 

De Boulle K, Verkerk AJMH, Reyniers E, Vits L, Hendricks J, Van Roy B, et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nature Genet 1993 3 31-35. 

Larson J, Jessen RE, Kim D, Fine AK, du Hoffmann J. 2005. Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein. J Neurosd 25 9460-9469. (Recent study using the LTP protocol in the APC slice)... 

A 6-year-old boy visits his physician because his parents have noticed autistic behavior and speech problems. The mother s family does have a history of mental retardation. Therefore, the physician suggested a genetic screen of the fragile X mental retardation 1 (FMRl) gene for fragile X syndrome. Polymerase chain reaction (PCR) revealed borderline fragile X syndrome. 

A. A complete loss of fragile X mental retardation protein (FMRP)... 

Translational control by 3 end binding is often used in developmental processes to inactivate a specific mRNA at certain developmental stages. Examples are the Pumilio protein (review Parisi and Lin, 2000) and the fragile X mental retardation protein (review Kaytor and Orr, 2001) which are sequence-specific RNA binding proteins that bind to short RNA motifs at the 3-end of specific mRNA thereby inhibiting mRNA translation. 

Valverde R, Pozdnyakova I, Kajander T, Venkatraman J, Regan L. Fragile X mental retardation syndrome stmcture of the KH1-KH2 domains of fragile X mental retardation protein structure. 2007 15 1090-1098. 

Darnell JC, Fraser CE, Mostovetsky O, Darnell RB. Discrimination of common and unique RNA-binding activities among fragile X mental retardation protein paralogs. Hum Mol Genet 2009 18 3164-77. 

Observational studies Tetracyclines, especially minocycline, inhibit the matrix metal-loproteinases (MMPs), and this has been studied in patients with the so-called fragile X syndrome (MIM 300624), an inherited form of intellectual disability and autism, with an estimated prevalence of about 1 in 4000 [125. The gene responsible is located on the X chromosome (Xq27.3) and is called Fragile X Mental Retardation-1 (FMRl MIM 309550) [126 ]. Minocycline improved behavioral performance and reduced anxiety in a FMRI knockout mouse [127 ], and has been studied in an open trial in 20 patients with the fragile X syndrome, aged 13-32 years [128 ]. The... 

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