Fragile X syndrome (FXS) is the most common inherited form of
intellectual disability (ID) and a known monogenic cause of
autism spectrum disorder (ASD). It is a trinucleotide repeat disorder, in which more than 200 CGG repeats in the
5' untranslated region (UTR) of the fragile X
mental retardation 1 (FMR1) gene causes methylation of the promoter with consequent silencing of the gene, ultimately leading to the loss of the encoded
fragile X mental retardation 1 protein, FMRP. FMRP is an
RNA binding protein that plays a primary role as a repressor of translation of various mRNAs, many of which are involved in the maintenance and development of neuronal synaptic function and plasticity. In addition to
intellectual disability, patients with FXS face several behavioral challenges, including anxiety, hyperactivity,
seizures, repetitive behavior, and problems with executive and language performance. Currently, there is no cure or approved medication for the treatment of the underlying causes of FXS, but in the past few years, our knowledge about the
proteins and pathways that are dysregulated by the loss of FMRP has increased, leading to clinical trials and to the path of developing molecular
biomarkers for identifying potential targets for
therapies. In this paper, we review candidate molecular
biomarkers that have been identified in preclinical studies in the FXS mouse animal model and are now under validation for human applications or have already made their way to clinical trials.