Aug 2026· Human Molecular Genetics· Vol 35 17· 0 citations
Medicine
TL;DR
This review critically evaluates the shift from traditional genetic screening to advanced epigenetic profiling as a robust framework for predicting ID in FXS and outlines a strategic roadmap for standardizing epigenetic assays, highlighting their potential to revolutionize the predictive landscape of neurodevelopmental disorders.
It is demonstrated that FMRP deficiency drives the aberrant translational upregulation of core m6A writers, a causal relationship definitively validated using CGG-corrected isogenic control lines and suggest a promising avenue for m6A-targeted therapies.
Lu Lu, Avijite Kumer Sarkar, Lan Dao et al.· Molecular Psychiatry· 0 citations
It is proposed that MDEMs are characterized by distributed, often subtle chromatin and gene expression perturbations, which impact diverse cellular pathways and processes and are frequently shared between distinct disorders, occupying an intermediate space between classical monogenic disorders and complex traits.
Leandros Boukas, Hans T Bjornsson· Epigenomics· 0 citations
An early-intervention approach, or combination of approaches, holds significant promise for transforming the lives of individuals affected by AS with outcomes dependent on their age or genotype.
C. Tychon, Theodora Markati, Serpil Alkan et al.· CNS Drugs· 0 citations
Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability. It is caused by a trinucleotide expansion in the 5' UTR of the Fragile X messenger ribonucleoprotein 1 (FMR1) gene leading to loss of expression of Fragile X messenger ribonucleoprotein (FMRP). There is currently no cure for FXS. We developed an FMR1 gene therapy based on an adeno-associated viral vector designed with strong translational potential for future clinical testing. The viral vector was tested in Fmr1 knockout mice using two translationally relevant delivery routes and ages corresponding to in utero, toddler, and adolescent ages in humans. Functional studies showed that the FMR1 gene therapy improved select translational FXS phenotypes spanning three critical domains: sensory hyperexcitability, adaptation to change, and altered brain activity. Expression after intracerebroventricular injection was most prominent in the forebrain, whereas intravenous delivery predominantly led to expression across midbrain and brainstem, suggesting that a dual route may be needed to achieve full brain coverage. Biodistribution analyses further suggested that FMRP expression must be titrated carefully for optimal rescue. In summary, we show that FMR1 gene therapy using delivery routes and vehicles approved for clinical use improves core phenotypes in a mouse model for FXS.
Richard K Lacher, Kari Henson, Lindsay N Wathen et al.· Gene Therapy· 0 citations
This review evaluates the potential of CRISPR-based editing as a therapeutic strategy for monogenic NDDs and evaluates the limitations that must be addressed before its widespread application in human patients.
Julia Mulles· American Journal of Student...· 0 citations
Findings link a population-enriched missense variant to disrupted chromatin regulation, genome stability, and neurodevelopmental timing, bridging human genetic risk with cellular pathophysiology.
R. Lease, Rediet T. Oshone, Yumna Ahmed et al.· Research Square· 0 citations