Genetics and Neurodevelopmental Disorders

A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome.

This paper describes a CRISPR/Cas9-based method to create a mouse model with a tandem duplication of Irak1 and Mecp2, which exhibits MDS-like neurological and immune phenotypes.

Mouse population genetics phenocopies heterogeneity of human Chd8 haploinsufficiency

The paper shows that incorporating genetic diversity into mouse models of neurodevelopmental disorders recapitulates human genetic and symptom heterogeneity associated with CHD8 haploinsufficiency.

Cortical interneuron development is affected in leukodystrophy 4H

This study investigates how 4H leukodystrophy mutations affect cortical interneuron development using induced pluripotent stem cells and finds reduced GABAergic synapses and altered interneuron markers.

SYNGAP1 deficiency disrupts neoteny in human cortical neurons in vivo.

This study shows that SYNGAP1 deficiency causes accelerated synaptic development and disrupted neoteny in human cortical neurons transplanted into mice, linking it to ID/ASD.

Impaired dendritic spike generation in the Fragile X prefrontal cortex is due to loss of dendritic sodium channels

The paper investigates dendritic spike generation in prefrontal cortex neurons of Fragile X mice and finds impaired sodium channel function leading to altered input-output transformation.

Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome

This study identifies impaired OTUD7A-Ankyrin regulation as a mechanism underlying neuronal dysfunction in 15q13.3 microdeletion syndrome using mouse and human models.

Neurodevelopmental disorder associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase

The paper identifies TAOK1 as a plasma membrane remodeling kinase and shows how mutations in it cause neurodevelopmental disorders by disrupting its membrane association and function.

Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X Syndrome

This study investigates synaptic integration in a mouse model of Fragile X Syndrome and finds sublinear summation of excitatory inputs in layer 5 pyramidal neurons, suggesting altered sensory and predictive input processing in ASD.

Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes

This study transplants FXS patient-derived neurons into mice to study their development and finds FMR1-dependent changes in synaptic activity and morphology.

Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy

The paper identifies STX1A variants causing a neurodevelopmental disorder with or without epilepsy, showing different phenotypes based on variant type.

Efficient delivery of FMR1 across the blood brain barrier using 2 AAVphp construct in adult FMR1 KO mice demonstrates the 3 feasibility of gene therapy for fragile X syndrome

This study demonstrates efficient brain-specific delivery of FMR1 via AAVphp vectors in adult FMR1 KO mice, leading to partial behavioral improvements and increased FMRP levels.

Regulation of excitatory presynaptic activity by Ambra1 protein determines neuronal networks in sex-dimorphic manner

This study shows that Ambra1 heterozygosity causes sex-specific reductions in excitatory synaptic activity, leading to E/I imbalance and autism-like behaviors in female mice.

Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome

This study shows that rats with Fragile X Syndrome exhibit impaired experience-dependent changes in hippocampal spatial activity and circuit function compared to wild-type rats.

Cell type-specific disruption of cortico-striatal circuitry drive repetitive patterns of behaviour in fragile X syndrome model mice

The paper investigates how cell-type-specific disruptions in cortico-striatal circuits in FXS model mice lead to repetitive behaviors and identifies potential therapeutic targets.

De Novo Variants in MRTFB have gain of function activity in Drosophila and are associated with a novel neurodevelopmental phenotype with dysmorphic features.

The paper identifies de novo MRTFB variants in humans linked to a neurodevelopmental disorder and shows their gain of function activity in Drosophila with specific phenotypes.

AUTS2 gene dosage affects synaptic AMPA receptors via a local dendritic spine AUTS2-TTC3-AKT-mTORC1 signaling dysfunction

This study shows that AUTS2 gene dosage affects synaptic AMPA receptors through the AUTS2-TTC3-AKT-mTORC1 pathway, leading to behavioral and cognitive impairments in mice.

Latent class analysis identifies distinctive behavioral subtypes in children with fragile X syndrome

The paper uses latent class analysis to identify distinct behavioral subtypes in children with fragile X syndrome, revealing clinically meaningful groups with unique cognitive and behavioral profiles.

A recurrent de novo splice site variant involving DNM1 alternative exon 10a causes developmental and epileptic encephalopathy through a dominant-negative mechanism

The paper identifies a recurrent de novo splice site variant in DNM1 exon 10a causing severe DEE through a dominant-negative mechanism, highlighting the importance of considering alternative isoforms in disease causation.

DPYSL2/CRMP2 isoform B knockout in human iPSC-derived glutamatergic neurons confirms its role in mTOR signaling and neurodevelopmental disorders

This study knocks out the DPYSL2-B isoform in human iPSC-derived neurons, showing reduced dendrite length and transcriptomic changes linked to mTOR signaling and schizophrenia.

CBP/EP300 acetylates and stabilizes the stress-responsive Heat Shock Factor 2, a process compromised in Rubinstein-Taybi syndrome

The paper shows that CBP/EP300 acetylates and stabilizes HSF2, which is disrupted in Rubinstein-Taybi syndrome, leading to impaired heat shock response.

Cell-type specific developmental defects in PTEN-mutant cortical organoids converge on abnormal circuit activity

The paper investigates how PTEN heterozygous mutations affect different cell types in human cortical organoids and shows that these effects lead to abnormal circuit activity regardless of genetic background.

Regulatory de novo mutations underlying intellectual disability

This study identifies regulatory de novo mutations in fetal brain-specific enhancers as a significant contributor to intellectual disability.

CHD8 Suppression Impacts on Histone H3 Lysine 36 Trimethylation and Alters RNA Alternative Splicing.

This study shows that CHD8 suppression reduces H3K36me3 levels and alters alternative splicing of ~2000 genes, linking CHD8 to RNA processing and ASD.

Fmrp regulates neuronal balance in embryonic motor circuit formation

This study shows that Fmrp regulates the proportion of neurons in embryonic motor circuits, with fmr1 mutants showing excess VeLD interneurons and synaptic defects.

A clustering of missense variants in the crucial chromatin modifier WDR5 defines a new neurodevelopmental disorder

The paper identifies six rare de novo missense variants in WDR5 associated with neurodevelopmental disorders and highlights their impact on COMPASS family protein interactions.

Juvenile Shank3 KO mice adopt distinct hunting strategies during prey capture learning

This study examines how juvenile Shank3 knockout mice differ in hunting strategies compared to wild-type mice, revealing behavioral patterns similar to those seen in individuals with autism spectrum disorder.

Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice

This study examines neuronal firing patterns in IRSp53-mutant mice during social approach, finding reduced variability and impaired social information encoding in the medial prefrontal cortex.

A non-canonical RNA-binding domain of the Fragile X protein, FMRP, elicits translational repression independent of mRNA G-quadruplexes

This study identifies a non-canonical RNA-binding domain in FMRP that mediates translational repression without requiring mRNA G-quadruplexes.

Autism-related behavioral phenotypes of three Camk2a mutant mouse lines with reduced CaMKIIalpha expression and/or activity

This study compares behavioral phenotypes of three Camk2a mutant mouse lines with reduced CaMKII expression or activity, finding increased stereotypic jumping, hyperactivity, and reduced tactile sensitivity across all lines.

MeCP2 represses the induction and maintenance of long-term synaptic plasticity

This study investigates MeCP2's role in long-term synaptic plasticity using Aplysia sensorimotor synapses, finding it inhibits gene expression needed for plasticity formation and maintenance.