Fragile X syndrome pathophysiology

It is thought that Fragile X syndrome is caused by mutation in a gene, specifically FMR1 gene present on X chromosome. The CGG triplet repetition leads to hypermethylation of the gene, which ultimately leads to silencing of the FMR1 gene. The FMR1 gene codes for protein responsible for brain development. Due to this defect, the normal neuron development is affected.

Fragile x syndrome has an x-linked dominant inheritance. It is caused by an expansion of CGG trinucleotide repeat within 5′ UTR in FMR1 gene on X chromosome. Due to high number of CGG repeats (>200), this leads to methylation of part of gene on X chromosome that codes for Fragile X Mental retardation protein (FMRP), which is required for proper development of connections between neurons.

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