Genetics and Neurodevelopmental Disorders

This study examines strain-dependent effects on neurobehavioral and seizure phenotypes in Scn2aK1422E mice, finding differences in anxiety-like behavior and seizure response between B6 and F1D2 backgrounds.

ZFP661 blocks cohesin trapping by CTCF and increases protocadherin diversity for proper cortical dendritic arborization.

This study identifies ARID1B's role in axon projection of callosal projection neurons, showing its haploinsufficiency leads to structural underconnectivity and agenesis of the corpus callosum.

The paper identifies a GCC repeat expansion in AFF3 as a significant cause of intellectual disability through a phenome-wide association study using DNA methylation profiling and UK Biobank data.

This study shows dFMRP recruits miRISC to repress translation of target mRNAs in Drosophila, independent of deadenylation and requiring AGO1 and GW182.

The paper investigates whether common cis-regulatory variants modify the penetrance of rare damaging coding variants in neurodevelopmental disorders using transcriptome-wide association and cis-eQTL analysis.

The paper compares clinical phenotypes of CHAMP1 mutations and deletions, finding mutations cause more severe symptoms through dominant negative or gain of function mechanisms, while deletions act via haploinsufficiency.

The paper presents clinical and molecular data on 65 individuals with SMARCC2-associated neurodevelopmental disorders, distinguishing phenotypes based on variant types and identifying potential pathomechanisms.

This study shows that phosphorylation of FMRP at S499 alters granule structure and function, affecting transport and translation in neurons.

The paper shows that human-specific genes SRGAP2B/C regulate synaptic neoteny in human cortical neurons by modulating SYNGAP1 levels.

The paper identifies monoallelic DHX9 variants as a cause of neurodevelopmental disorders and Charcot-Marie-Tooth disease, showing genotype-phenotype correlations and cellular dysfunction.

This study shows that Mecp2 knock-out astrocytes reduce synaptic density by secreting IL-6, which can be mitigated by blocking IL-6 activity.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

The paper investigates the effects of different HCFC1 mutations in zebrafish on mTor activity and radial glial cell phenotypes, revealing differential outcomes linked to mutation type.

The paper identifies shared regulatory targets of autism-associated transcriptional regulators in brain-expressed genes and shows their functional convergence in neurodevelopmental outcomes.

The paper identifies ZMYM3 variants in 22 individuals with neurodevelopmental delay, showing recurrent mutations, phenotypic overlap, and functional effects, supporting ZMYM3 as a novel NDD gene.

This study shows that reducing SYNGAP1 in inhibitory interneurons disrupts sensory representations in the neocortex and causes learning deficits in mice.

The paper introduces an optimized methodology combining DiI and immunofluorescence to study hippocampal spine synapses in Fmr1 KO mice, revealing structural abnormalities associated with Fragile X Syndrome.

The paper investigates FMRP expression in human nociceptor axons of the spinal dorsal horn, finding it colocalizes with pain-related markers and suggests a role in sex dimorphic chronic pain mechanisms.