How+does+Fragile-X+become+expressed?

__How does Fragile-X Syndrome manifest itself?__
Fragile-X Syndrome is caused by the FMR1 gene. The disorder occurs when a mutation occurs in the gene in one of two ways; when the gene suffers a deletion or when the gene suffers a hypermethylation. Both circumstances cause the gene product of FMR1, FMRP, to be nonexistant (Garber, 2008). In the case of the deletion, the FMR1 gene is not complete and unable to synthesize the gene product for use (Coffee, 2008). While in the hypermethylation, the trinucleotide sequence of CGG that is normally repeated about 23 times in a healthy human being is mutated and causes 200 or more repeats of the CGG sequence. This hypermethylation causes a silencing effect of the FMR1 gene and inhibits it from producing FMRP.

__What is FMRP?__
FMRP is the gene product of FMR1 that is a selective RNA-binding protein which negatively regulates protein synthesis in neuronal dendrites. Without it, the transcripts that are normally regulated by FMRP become over translated. The saturation of certain proteins results in decreased dendrite synapse strength due to AMPA receptor trafficking abnormalities which. in part, lead to the fragile-X syndrome phenotype (Garber, 2008).



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