Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by expansion mutation in the FMR1 gene, which leads to gene silencing via imprinting. Fmr1, located on the X chromosome, encodes the protein FMRP, a pivotal protein for neurogenesis in cortical development (Saffary and Xie, 2011; Casingal et al., 2020). Interestingly, female FXS premutation carriers, especially those with a paternal lineage of the premutation, exhibit an increased incidence of premature ovarian failure (Hundscheid et al., 2000). Despite these findings, the impact of FMRP absence on imprinting mechanisms in the brain remain obscure. Our research utilized RNA sequencing to delineate gene expression changes during cortical development in the absence of FMRP. We analyzed the telencephalon of wild-type (WT) and Fmr1-knockout (KO) mouse embryos at the embryonic day 14.5 (E14.5), identifying differentially expressed genes (DEGs) and their sex-specific patterns. In the telencephalon of female Fmr1-KO embryos, we observed 16 downregulated genes and 17 upregulated genes (p<0.05; Fold change>1.5). Notably, a certain paternally expressed gene exhibited a marked decrease in its expression in female Fmr1-KO telencephalon. This finding was further corroborated by quantitative real-time PCR of E14.5 cortices. Additionally, in situ hybridization revealed a disrupted expression pattern of the implicated gene in the E14.5 telencephalon. These data hint at a potential role of FMRP in regulating gene imprinting in a parent-of-origin-specific manner. Our study invites further exploration into a new role of FMRP yet to be discovered underlying FXS pathogenesis and symptomatology.