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Fragile X Syndrome and Infertility: Genetic, Epigenetic, and Clinical Perspectives
Zeynep Hayırlıoğlu1, Zeliha Yücel2, Emine Berrin Yüksel31Department of Histology and Embryology,Health Sciences Institute, Selçuk University, Konya, Turkey2Department of Neurology, School of Medicine, Karamanoglu Mehmetbey University, Karaman, Turkey
3Department of Medical Genetics, School of Medicine, Karamanoglu Mehmetbey University, Karaman, Turkey
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and is closely associated with autism spectrum disorder. It results from the expansion of CGG repeats in the FMR1 gene, leading to hypermethylation and silencing of gene expression, ultimately causing the absence of Fragile X Mental Retardation Protein (FMRP). This protein is essential for synaptic plasticity, neuronal function, and various physiological processes, including reproductive health. While cognitive and behavioral impairments are well-documented, the impact of FXS on reproductive function remains underexplored.
Individuals carrying the full mutation or premutation (55–200 CGG repeats) often experience significant reproductive challenges. Female premutation carriers are at risk of Fragile X-associated primary ovarian insufficiency (FXPOI), leading to infertility and early menopause. Males with FXS frequently exhibit spermatogenic failure, characterized by reduced sperm count and motility due to FMRP deficiency, contributing to infertility. Epigenetic modifications, including DNA methylation and histone alterations, further influence gene expression and clinical variability.
This review explores the genetic and epigenetic mechanisms underlying FXS and their impact on reproductive health. Additionally, current diagnostic and clinical strategies, including genetic counseling, fertility preservation, and assisted reproductive technologies, are discussed. Advancements in gene editing and epigenetic therapies hold promise for mitigating the reproductive effects of FXS. Understanding these mechanisms is crucial for improving clinical management and reproductive outcomes in affected individuals.
Manuscript Language: English