Article

Fragile X syndrome: Causes, diagnosis, mechanisms, and therapeutics

The Journal of clinical investigation (Impact Factor: 13.22). 12/2012; 122(12):4314-22. DOI: 10.1172/JCI63141
Source: PubMed

ABSTRACT

Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders. FXS is caused by a triplet expansion that inhibits expression of the FMR1 gene; the gene product, FMRP, regulates mRNA metabolism in the brain and thus controls the expression of key molecules involved in receptor signaling and spine morphology. While there is no definitive cure for FXS, the understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS. Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families.

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    • "Fragile X syndrome (FXS) is a rare genetic disorder, mostly characterized by moderate to severe mental retardation, autistic and hyperactive behaviour, macroorchidism, large ears, a prominent jaw, and high-pitched jocular speech [1]. Neuropathological features of the fragile X syndrome are long, thin, and sinuous dendritic spines, increased intracranial volume, enlarged ventricles, increased volumes of selective subcortical grey matter regions, decreased size of "
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    • "It is thought that this is achieved through binding of the mRNA by the FMR protein [23] [25]. While the brain and the nervous system have been the focus of studies on FMR function [21] [23] [25], recent studies have begun to add to the knowledge of FMRs role in other contexts. For example, it was recently demonstrated that the FMR1 gene is up-regulated in cancer cells like the hepatocellular carcinoma where it aids in tumor migration and metastasis [26]. "
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    • "fmr1 [fragile X mental retardation 1] knockout mice, Black and Tan BRachyury (BTBR) mice, and valproic acid-treated rats), that display autistic-like features. Fragile X syndrome (FXS) is an inherited disorder caused by mutations in the fmr1 gene, that is translated into the fragile X mental retardation 1 protein (FMRP), that in turn plays a role in the development of synapses [97] [98]. Expansion mutations of the fmr1 gene produce autistic features in approximately 40% of FXS patients, and thus FXS provides a valuable model for identifying novel biomarkers/targets for autism and for dissecting the underlying neurochemical pathways [99]. "
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