Genetics and Neurodevelopmental Disorders

Exploring Single-Cell Gene Regulatory Dynamics in Rett Syndrome

This study uses single-cell transcriptomic data from human patients to analyze gene regulatory dynamics in Rett syndrome, identifying master regulators and potential therapeutic targets.

Human patient-specific FOXG1 syndrome mouse model revealed FOXG1-MYCN-mediated regulation of protein homeostasis in neurodevelopmental disorder

This study creates a patient-specific mouse model of FOXG1 syndrome and identifies disrupted protein homeostasis and neuroinflammation as key factors in the disorder's pathogenesis.

Cooperative behavior in rat dyads reveals distinct social coordination strategies of increasing complexity

This study investigates cooperative behavior in rat dyads, identifying distinct social coordination strategies and deficits in Fmr1 knockout rats, a model of Fragile X syndrome.

TBCK Deficiency Alters Ribosomal Function, RNA Splicing, and miRNA Networks: Insights from Multi-Omics Analyses

This study uses multi-omics analyses to show that TBCK deficiency disrupts ribosomal function, RNA splicing, and miRNA networks in TBCK-/- cells, providing insights into the molecular mechanisms of the disorder.

Individuals with intellectual disability have an increased burden of de novo variants in cis-regulatory elements of glutamatergic neurons.

PEDF peptides rescue defects in neurite morphogenesis and intracellular calcium response in cortical neurons from mice exposed to valproic acid

PEDF peptides improve neurite formation and calcium response in VPA-exposed cortical neurons, suggesting potential therapeutic use for neurodevelopmental disorders.

Epigenome and transcriptome changes in KMT2D-related Kabuki syndrome Type 1 iPSCs, neuronal progenitors and cortical neurons

This study examines epigenome and transcriptome changes in KS1 iPSCs and neuronal differentiation stages, identifying altered H3K4 methylation and gene expression patterns.

Cell type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development

This study identifies cell type-specific gene expression changes in Chd8 haploinsufficient mouse cortex during development, highlighting dysregulation in progenitors and neurons.

Impaired thalamic burst firing in Fragile X syndrome

This study identifies impaired thalamic burst firing in a mouse model of Fragile X syndrome, linking it to altered voltage sensitivity of Ca2+-dependent low threshold spikes.

Hypoplasticity in sensory-driven necortical circuits of Fragile X mice

This study shows that LTP in sensory cortex is impaired in Fragile X mice, leading to hypoplasticity in layer 2/3 pyramidal neurons and altered somatosensory processing.

Whole-brain clearing reveals region- and cell type-specific imbalances in inhibitory neurons in a mouse model for Kleefstra Syndrome

The paper uses whole-brain clearing and imaging to identify region- and cell type-specific changes in GABAergic neurons in a mouse model of Kleefstra Syndrome.

Erythropoietin alleviates intellectual disability and autism-like behavior of mice caused by Zbtb20 haploinsufficiency, a construct-valid model of Primrose syndrome

This study shows that erythropoietin treatment improves behavioral and phenotypical symptoms in Zbtb20+/- mice, a model of Primrose syndrome.

CA2 neurons show abnormal responses to social stimuli in a rat model of Fragile X syndrome

The paper examines CA2 neuronal responses to social stimuli in a rat model of Fragile X Syndrome and finds impaired responses despite normal social behaviors.

Scheduled feeding improves behavioral outcomes and reduces inflammation in a mouse model of Fragile X syndrome.

Sex differences in the developing human cortex intersect with genetic risk of neurodevelopmental disorders

The paper identifies sex-biased molecular vulnerabilities in the developing human cortex linked to neurodevelopmental disorders by integrating transcriptomic and epigenomic data with mutation analysis.

Delayed development of inner hair cell ribbon synapses in a mouse model of fragile X syndrome

The paper examines delayed maturation of inner hair cell ribbon synapses in Fmr1 KO mice, linking it to auditory circuit development issues.

Deciphering the mechanistic basis for the pathological effect of the Gαo E246K mutation in neurodevelopmental disorder

The paper investigates the molecular mechanism of the Gαo E246K mutation in neurodevelopmental disorders, showing it disrupts the GTPase cycle by impairing Gβγ dissociation, leading to dominant-negative effects.

Translational reading frame determines the pathogenicity of C-terminal frameshift deletions in MeCP2: an alternative therapeutic approach

The paper identifies that C-terminal deletions in MECP2 cause Rett syndrome by reducing MeCP2 levels due to a specific reading frame shift, and shows a gene-editing strategy to correct this.

Dysregulation of an H3K79me2-dependent epigenetic barrier impairs neural progenitor cell proliferation and differentiation in Fragile X syndrome

This study identifies an H3K79me2-dependent epigenetic barrier in FXS neural progenitor cells, showing its dysregulation impairs proliferation and differentiation.

Brain Mecp2 Gene Dosage and Gene Therapy Shape Multi-Omic Signatures and Putative Biomarkers in Rett Syndrome

The paper identifies cross-species biomarkers and mechanisms in Rett Syndrome using gene therapy and multi-omic analysis in mice.

Learning Impairments in Fmr1-/- mice on an Audio-Visual Temporal Pattern Discrimination Task.

This study shows Fmr1-/- mice have learning impairments in a temporal pattern discrimination task, with reduced performance on audiovisual stimuli compared to wild-type mice.

Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling

The paper identifies pathogenic TMEM184B variants in six pediatric cases and shows they disrupt metabolic signaling and neural development through functional studies in zebrafish and human cells.

Nonsense, but not frameshift, truncating mutations result in Cyclin D2 stabilisation in an induced pluripotent stem cell model of MPPH

The paper shows that a nonsense mutation in CCND2 stabilizes Cyclin D2 in iPSC models of MPPH, while frameshift mutations do not, affecting neurogenesis.

Cyclin-dependent kinase-like 5 (CDKL5) binds to talin and is anchored at the postsynaptic density via direct interaction with PDZ domains

This paper identifies how CDKL5 is anchored at the postsynaptic density via interactions with PDZ domains and talin, and shows that its spatial positioning is regulated by talin's mechanical properties.

Neurobehavioral Signatures in Overgrowth Intellectual Disability Syndromes: Dissecting Genotype-Phenotype Relationships in the PI3K-AKT-MTOR Pathway

The paper compares neurobehavioral profiles of Smith-Kingsmore Syndrome and PTEN Hamartoma Tumor Syndrome, identifying distinct features and diagnostic markers.

Syngap1 regulates the synaptic drive and membrane excitability of Parvalbumin-positive interneurons in mouse auditory cortex

This study investigates how Syngap1 haploinsufficiency in GABAergic interneurons affects synaptic and intrinsic properties in mouse auditory cortex, linking these changes to auditory processing deficits in SYNGAP1-ID.

Biallelic variants in the non-coding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes

The paper identifies biallelic variants in RNU4-2 causing a recessive neurodevelopmental syndrome with distinct white matter changes, expanding the known genotypic and phenotypic spectrum of RNU4-2-related disorders.

Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories

This paper screens autism-associated genes in C. elegans to identify their impact on GABA neuron remodeling and behavior, revealing distinct developmental trajectories and new molecular mechanisms.

Wide-ranging behavioral dysfunction in two mouse models of pathological human variants in the GRIK2 kainate receptor gene

This study creates mouse models of GRIK2 variants causing neurodevelopmental disorders and finds they exhibit behavioral and seizure-related impairments similar to humans.

A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.

This study examines the molecular and behavioral effects of MYT1L haploinsufficiency in mice, finding region-specific hypothalamic disruptions and sex-specific behavioral stability.