Genetics and Neurodevelopmental Disorders

Altered axonal initial segment development links circuit and Kv7 dysfunction in an Fmr1 knockout rat

This study shows that Fmr1 knockout rats exhibit early Kv7 channel dysfunction in CA1 neurons due to altered axon initial segment development, which recovers by adulthood.

CK2 variant function and disease modelling in Drosophila reveal allelic heterogeneity and Wnt/β-catenin-mediated phenotypes

The paper uses Drosophila to model CK2 variants causing neurodevelopmental disorders, finding loss- and gain-of-function effects and Wnt/β-catenin-mediated phenotypes.

A serotonergic mechanism is involved in the pro-cognitive effect of AM6545 treatment in a mouse model of fragile X syndrome

This study shows that AM6545 treatment improves cognitive deficits in FX mice by modulating serotonergic receptors and gut microbiota.

Preserved social development but impaired executive function in a Shank3-deficient rat model of Phelan-McDermid syndrome

This study examines Shank3-deficient rats to identify behavioral impairments, finding that executive dysfunction is more pronounced than sensorimotor or social deficits.

A CK2α-G3BP1 signaling axis regulates local translation in developing neurons and is disrupted in OCNDS

This study identifies a CK2α-G3BP1 signaling axis critical for neuronal translation and development, showing its disruption causes OCNDS pathology.

Postnatal Sensory Experience and Barrel Cortex Alterations Anticipate Autistic Traits in a Mouse Model of Cdkl5 Deficiency Disorder

This study shows that CDKL5 deficiency in mice leads to sensory processing defects in the barrel cortex and autistic traits, which can be rescued by neonatal CDKL5 replacement.

Dominant truncating variants in KAT6A cause two neurodevelopmental disorders with opposite gene regulatory and metabolic changes

This paper identifies that truncating variants in KAT6A cause two distinct neurodevelopmental disorders with opposing gene regulatory and metabolic effects, highlighting the need for variant-level stratification in therapy development.

Modeling and targeting haploinsufficiency in SHINE syndrome

This study models DLG4 mutations in SHINE syndrome using iPSC-derived neurons, showing PSD-95 deficiency and electrophysiological changes, and demonstrates rescue via AAV9-mediated gene delivery.

Aberrant expression of stress-related Hsrω-n lncRNA contributes to CGG repeat-mediated toxicity in a Drosophila model of FXTAS

This study identifies Hsr{omega}-n lncRNA as a mediator of CGG repeat toxicity in a Drosophila FXTAS model, showing its overexpression exacerbates neurodegeneration while its reduction alleviates it.

Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development

This study investigates how pathogenic KIF1A variants affect axonal trafficking and synaptic development in human neurons using gene-edited iPSCs.

Early AMPA receptor potentiation modifies synaptic maturation and disease progression in Rett models

This study evaluates the effects of early AMPA receptor potentiation in Rett syndrome models, finding that early treatment improves survival, motor function, and cognition, while later treatment is less effective.

Cross-species analysis of GNB1 I80T encephalopathy: conserved developmental, epileptic and neuronal transcriptome signatures

This study identifies conserved transcriptomic signatures in GNB1 encephalopathy across human and mouse models, linking GNB1 mutations to developmental, epileptic, and neuronal dysfunction.

Truncated ASXL3 Alters Chromatin Accessibility and Epigenetic Landscape in Bainbridge-Ropers Syndrome Suggesting a Gain-of-Function Etiology

Patient-derived neuronal models and mouse models reveal that truncated ASXL3 drive epigenetic dysregulation through a gain-of-function mechanism.

Autism-associated NRXN1α deletion rewires the H3K27me3 landscape and epigenetically disrupts human neural induction.

This study shows that NRXN1 deletion alters the H3K27me3 landscape and disrupts neural induction through epigenetic changes and spliceosome dysregulation.

Biallelic protein truncating EXOSC6 variants cause a neurodevelopmental disorder with cerebellar atrophy, ataxia, and global developmental delay

The paper reports a patient with a neurodevelopmental disorder caused by biallelic EXOSC6 variants, expanding the known spectrum of exosomopathies.

Disrupted Developmental Trajectory of Ultrasonic Vocalizations in a Rat Model of Fragile X Syndrome

This study examines how Fmr1 mutation affects the developmental trajectory of ultrasonic vocalizations in rats, finding reduced call numbers and delayed syntactic complexity in Fmr1 knockout pups.

Single-nucleus transcriptomics reveal disrupted pathways in the prefrontal cortex of Scn2a-deficient mice

This study uses snRNA-seq to analyze gene expression changes in Scn2a-deficient mice, identifying disrupted pathways in neuronal subtypes of the prefrontal cortex.

Impaired astrocyte-to-neuron cholesterol trafficking drives synaptic dysfunction in Rett syndrome

Mecp2 knock-out mouse astrocytes accumulate cholesterol yet release poorly lipidated ApoE; cholesterol supplementation restores synaptic puncta density in neurons exposed to their conditioned medium and in Mecp2 heterozygous neurons.

Allele-specific rescue of neurexin behavioral phenotypes by monoamine-targeting compounds

This study identifies monoamine-targeting compounds that rescue neurexin-related behavioral phenotypes in C. elegans and Drosophila, with olanzapine showing broad efficacy across genetic backgrounds.

Brain-wide circuitry underlying altered auditory habituation in zebrafish models of autism.

The paper investigates auditory habituation differences in zebrafish autism models, finding unique and shared brain-wide circuit changes across genetic lines.

Characterization of Electrophysiological and Transcriptomic Alterations in Patient-Derived Neurons from CHAMP1 Syndrome

This study investigates CHAMP1 mutations' effects on neuronal development using patient-derived neurons, revealing disruptions in DNA repair, membrane excitability, and synaptic connectivity.

Unconstrained Plasticity Disrupts Memory Consolidation in a Mouse Model of Rett Syndrome

This study identifies excessive and ectopic synaptic plasticity in RTT mice as a cause of memory impairment by disrupting stable neural representations.

SETD5 dysfunction in human astrocytes drives IL-6-mediated neuronal impairments via the JAK/STAT signaling pathway

This study shows that SETD5 dysfunction in astrocytes increases IL-6, which harms neurons via JAK/STAT signaling, suggesting therapeutic targeting of this pathway for ASD and ID.

Comparative Analysis of FOXP2 Expression in the Thalamus of Mice, Rats, and Macaques: Implications for the Evolution of Language Circuits.

This study compares FoxP2 expression in thalamic nuclei across mice, rats, and macaques, finding species-specific patterns that suggest a role in language circuit evolution.

FMRP safeguards long mRNA expression by opposing repressive RNP states

The paper shows FMRP protects long mRNAs from repression by Me31B/DDX6, challenging the view of FMRP as a translational repressor.

Pathogenic MAPK8IP3 variants drive distinct motor and behavioral phenotypes in humans and mice

The paper compares clinical and behavioral effects of different MAPK8IP3 variants in humans and mice, showing shared and distinct phenotypes linked to specific protein domains.

DROSOPHILA PRICKLE MUTANTS DISPLAY COMORBID NEUROLOGICAL PHENOTYPES AND PROVIDE A GENETIC LINK BETWEEN EPILEPSY AND AUTISM SPECTRUM DISORDER

This study shows that Drosophila prickle mutants exhibit ASD-like behaviors and neurological anomalies, linking PRICKLE function to both epilepsy and autism spectrum disorder.

Sensory experience and mTORC1 interplay orchestrates the maturation of cortical interneuron connectivity and tactile sensitivity

This study shows that mTORC1 dysregulation in PV interneurons affects tactile sensitivity and social behavior by altering connectivity and excitability.

ASXL3 truncating patient variants mediate transcriptional gain-of-function and are antisense oligonucleotide-responsive

The paper shows ASXL3 truncating variants cause disease via gain-of-function, not loss-of-function, and demonstrates antisense oligonucleotides can reverse the transcriptional effects.

Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model

Therapeutic siRNAs provide safe and durable modulation of MECP2 for the treatment of mild and severe MECP2 Duplication Syndrome.