Journal of Clinical Epigenetics Open Access

The Epigenetic Effects on Fragile X Syndrome

Becking Stone^* Department of Biological Sciences, Washington State University, USA
^*Correspondence: Becking Stone, Department of Biological Sciences, Washington State University, USA, Email:

Received: 30-Aug-2023, Manuscript No. ipce-23-18125; Editor assigned: 01-Sep-2023, Pre QC No. ipce-23-18125 (PQ); Reviewed: 15-Sep-2023, QC No. ipce-23-18125; Revised: 20-Sep-2023, Manuscript No. ipce-23-18125 (R); Published: 27-Sep-2023, DOI: 10.21767/2472-1158-23.9.85

Introduction

Fragile X syndrome (FXS) is a complex genetic disorder that affects cognitive and behavioural development. It is the leading inherited cause of intellectual disability and autism spectrum disorders. While FXS is primarily associated with mutations in the FMR1 gene, recent research has shown that epigenetic modifications play a crucial role in the manifestation and severity of the syndrome. This article explores the epigenetic effects on Fragile X syndrome, shedding light on how these modifications impact its clinical presentation and potential therapeutic avenues.

Description

Fragile X syndrome is caused by a mutation in the FMR1 gene located on the X chromosome. In individuals with FXS, a CGG trinucleotide repeat in the FMR1 gene is expanded beyond a certain threshold. When this expansion occurs, it triggers a cascade of events that leads to the transcriptional silencing of the FMR1 gene, resulting in a deficiency of the Fragile X Mental Retardation Protein (FMRP). FMRP is crucial for the regulation of synaptic plasticity and protein translation in the brain. Its absence or shortage has profound effects on neurodevelopment, leading to the core features of FXS, including intellectual disability, social anxiety, repetitive behaviours, and hypersensitivity to sensory stimuli. Epigenetics refers to heritable changes in gene expression or cellular phenotype that do not involve alterations in the DNA sequence itself. Epigenetic modifications, such as DNA methylation and histone modifications, play a significant role in regulating gene expression. In the context of Fragile X syndrome, epigenetic modifications influence the transcriptional regulation of the FMR1 gene, impacting its expression and, consequently, the severity of the syndrome. DNA methylation is a well-studied epigenetic modification that involves the addition of a methyl group to the cytosine base of DNA. In individuals with FXS, the FMR1 gene’s promoter region is often hypermethylated. This hypermethylation effectively silences the gene, preventing its normal transcription and translation. Consequently, the deficiency of FMRP exacerbates the cognitive and behavioural symptoms associated with FXS. Histones are proteins that package and organize DNA into chromatin, regulating gene accessibility. Altered histone modifications can also influence the expression of the FMR1 gene. In particular, histone hypoacetylation and H3K9me2 (methylation of histone H3 at lysine 9) are associated with gene silencing in FXS. Epigenetic changes in histone modifications, along with DNA methylation, contribute to the transcriptional silencing of FMR1. The epigenetic regulation of the FMR1 gene has a direct impact on the clinical presentation of Fragile X syndrome. The extent of DNA methylation and histone modifications in the FMR1 gene promoter can vary among affected individuals. Those with higher levels of methylation tend to exhibit more severe symptoms of FXS, including lower IQ, increased social anxiety, and heightened sensory sensitivities. Additionally, epigenetic changes may account for some of the clinical variability observed in FXS. In cases of mosaicism, where some cells have normal FMR1 gene activity and others have silenced genes, the clinical presentation can be milder than in individuals with a fully methylated FMR1 gene. This suggests that the epigenetic landscape can differ even within the same individual, which can complicate the diagnosis and treatment of FXS. Understanding the epigenetic effects on Fragile X syndrome opens the door to potential therapeutic strategies that target these modifications.

Conclusion

Fragile X syndrome is a complex genetic disorder with significant variability in its clinical presentation. While the underlying genetic mutation in the FMR1 gene is well-established, epigenetic modifications play a crucial role in the severity and variability of FXS. DNA methylation and histone modifications silence the FMR1 gene, leading to a deficiency of FMRP and the core features of the syndrome.