Article Sections

Introduction

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a significant genetic cause of autism spectrum disorder (ASD).  It is an X-linked disorder caused by a mutation in the FMR1 gene on the X chromosome.

Pathogenesis

FXS is due to an unstable CGG trinucleotide repeat expansion in the FMR1 gene on the long arm of the X chromosome ( Figure 1).  FMR1 normally has 6-50 CGG trinucleotide repeats in the 5′ untranslated region that can potentially expand during meiosis in oocytes.  Expansion over generations can lead to >200 CGG trinucleotide repeats (ie, full mutation).  This mutation causes hypermethylation of the gene, which silences the gene and prevents transcription of the associated fragile X messenger ribonucleoprotein (FMRP).  Because FMRP is involved in the development and plasticity of neurons, silencing of the gene in FXS results in impaired neural development.

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Figures

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Tables

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