Genetics and Neurodevelopmental Disorders

Analyses of the Autism-associated Neuroligin-3 R451C Mutation in Human Neurons Reveals a Gain-of-Function Synaptic Mechanism

The paper investigates the impact of the NLGN3 R451C mutation on human neurons, finding it reduces protein levels but enhances excitatory synapses, potentially contributing to ASD pathogenesis.

Transcriptional and functional consequences of alterations to MEF2C and its topological organization in neuronal models

The paper investigates the effects of MEF2C mutations and chromatin structural variants on transcriptional and functional outcomes in neuronal models, revealing differential impacts based on mutation type and chromatin topology.

Missense and nonsense mutations of the zebrafish hcfc1a gene result in contrasting mTor and radial glial phenotypes.

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.

Wide spectrum of neuronal and network phenotypes in human stem cell-derived excitatory neurons with Rett syndrome-associated MECP2 mutations

This study examines the effects of MECP2 mutations on neuronal and network phenotypes in human stem cell-derived excitatory neurons, showing a spectrum of morphological, electrophysiological, and circuitry changes based on mutation severity.

Autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes.

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

Evaluation of Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome

The paper evaluates Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome by reviewing literature and presenting data showing its inhibition normalizes neuron function and behavior in mouse models.

Adult Camk2a gene reinstatement restores the learning and plasticity deficits of Camk2a knockout mice

This study shows that restoring CAMK2A expression in adult Camk2a knockout mice rescues learning and plasticity deficits, indicating that CAMK2A is not essential for irreversible neurodevelopment.

Function of FMRP domains in regulating distinct roles of neuronal protein synthesis

This study identifies the functional roles of FMRP domains in translation regulation, showing that the C-terminus mediates ribosome binding and repression, while domain synergy is needed for granule formation and microtubule association.

Deleterious, protein-altering variants in the X-linked transcriptional coregulator ZMYM3 in 22 individuals with a neurodevelopmental delay phenotype

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.

Interneuron-targeted disruption of SYNGAP1 alters sensory representations in neocortex and impairs sensory learning

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

Large deletions perturb peripheral transcriptomic and metabolomic profiles in Phelan-McDermid syndrome

This study identifies molecular differences between PMS patients with small and large deletions, showing reduced cytotoxic cell signatures and sphingolipid metabolism in large deletions.

Regulation of Liprin-α phase separation by CASK is disrupted by a mutation in its CaM kinase domain

The paper shows that a mutation in CASK's CaMK domain disrupts its regulation of Liprin-α phase separation, leading to neurodevelopmental disorder with microcephaly and pontocerebellar hypoplasia.

Combined DiI and antibody labeling reveals complex dysgenesis of hippocampal spine synapses in a mouse model of Fragile X Syndrome.

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.

Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

This study identifies 18 high-confidence genetic variants in 26% of childhood apraxia of speech cases, expanding the list of candidate genes and highlighting shared pathways with other neurodevelopmental disorders.

Absence of the fragile X mental retardation protein alters response patterns to sounds in the auditory midbrain

This study examines how the absence of Fmr1 affects auditory response patterns in the Inferior Colliculus of mice, identifying changes linked to acoustic hypersensitivity.

Fragile X Mental Retardation Protein (FMRP) expression in human nociceptor axons of the spinal dorsal horn-- Implications for RNA targeting and localized translation

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.

Aberrant astrocyte protein secretion contributes to altered neuronal development in diverse disorders

The paper identifies disorder-specific and shared changes in astrocyte protein secretion and gene expression in neurodevelopmental disorders, linking increased Igfbp2 and BMP signaling to altered neuronal development.

Expanding the Phenotypic spectrum of NAA10-related neurodevelopmental syndrome and NAA15-related neurodevelopmental syndrome

The paper expands the phenotypic spectrum of NAA10 and NAA15-related neurodevelopmental syndromes by analyzing clinical data from 106 NAA10 and 66 NAA15 variant carriers, revealing variable severity and multi-system involvement.

Convergent Cerebrospinal Fluid Proteomes and Metabolic Ontologies in Humans and Animal Models of Rett Syndrome

The paper identifies shared proteomic and metabolic ontologies in Rett syndrome across species and validates them as potential biomarkers.

Gain and loss of function variants in EZH1 disrupt neurogenesis timing and cause overlapping neurodevelopmental disorders

Shared and distinct functional effects of patient-specific Tbr1 mutations on cortical development

This study examines the functional effects of two patient-specific Tbr1 mutations on cortical development in mice, revealing both shared and distinct phenotypes.

mGluR5 PAMs rescue cortical and behavioural defects in a mouse model of CDKL5 deficiency disorder.

This study shows that mGluR5 positive-allosteric modulators correct synaptic and behavioural defects in a CDKL5 deficiency disorder mouse model and human patients.

Mouse and cellular models of KPTN-related disorder implicate mTOR signalling in cognitive and progressive overgrowth phenotypes

The paper investigates KPTN-related disorder using mouse and human stem cell models, identifying mTOR pathway dysregulation as a key mechanism underlying cognitive and overgrowth phenotypes.

Increased reliability of visually-evoked activity in area V1 of the MECP2-duplication mouse model of autism

The paper finds increased reliability of visually-evoked activity in V1 neurons of MECP2-duplication mice, suggesting altered sensory processing mechanisms in autism.

Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy and periventricular calcifications

Dichotomous Intrinsic Properties of Adult Accumbens Medium Spiny Neurons Vanish in the Fragile X Mouse Model of Autism

The paper compares intrinsic properties of D1- and D2-MSNs in FXS mice and finds they lose their distinct characteristics, leading to a uniform phenotype.

De Novo, Post-Zygotic, Inter-Tissue Mosaicism of Cell Autonomous ADNP Mutations in Autistic Individuals: Restricted Environmental Contribution

The paper quantifies ADNP mutation mosaicism across tissues in a post-mortem autistic individual, showing post-zygotic, tissue-specific mutation patterns and ruling out environmental factors.

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome Model

This study uses single-cell RNA sequencing to analyze a FXS mouse model, revealing cell-type specific dysregulation and potential mTOR pathway differences.

Defective synaptic plasticity in a model of Coffin-Lowry Syndrome is rescued by simultaneously targeting PKA and MAPK pathways

The paper shows that combining PKA and MAPK pathway activators rescues synaptic plasticity deficits in a CLS model by synergistically restoring RSK phosphorylation and LTF.

Indepth characterization of a cohort of individuals with missense and loss-of-function variants disrupting FOXP2

This study characterizes 29 individuals with FOXP2 variants, showing high prevalence of speech disorders and language impairments, with relatively specific phenotypes compared to other monogenic conditions.