Genetics and Neurodevelopmental Disorders

Counter-balancing X-linked Mecp2 hypofunction by hyperfunction ameliorates disease features in a model of Rett syndrome: implications for genetic therapies

In a mouse model of Rett syndrome, counterbalancing mosaic LOF with complementary mosaic GOF improves phenotypic outcome.

Disruption of the autism-associated gene SCN2A alters synaptic development and neuronal signaling in patient iPSC-glutamatergic neurons

This study examines how different SCN2A de novo variants affect human neuron development and function using patient-derived iPSCs.

Hao-Fountain Syndrome: 32 novel patients reveal new insights into the clinical spectrum

This study reports on 32 novel patients with Hao-Fountain syndrome, expanding the clinical understanding of the disorder and identifying new phenotypic features and genotype-phenotype correlations.

Connectomic and behavioral alterations in creatine transporter deficiency are partially normalized by gene therapy

This paper investigates brain network and behavioral changes in a mouse model of CTD and shows that perinatal gene therapy can partially reverse some symptoms but not all.

Multidimensional analysis of a social behavior identifies regression and phenotypic heterogeneity in a female mouse model for Rett syndrome

The paper identifies two distinct behavioral phenotypes in a female mouse model of Rett syndrome using multidimensional analysis and DeepLabCut, showing age- and context-dependent regression.

EHMT2 LOSS-OF-FUNCTION ALTERATIONS CAUSE A KLEEFSTRA-LIKE SYNDROME

The paper identifies a de novo EHMT2 mutation causing a Kleefstra-like syndrome by reducing enzyme activity and altering epigenetic profiles.

An inappropriate decline in ribosome levels drives a diverse set of neurodevelopmental disorders

The paper identifies how reduced ribosome levels in neural progenitor cells contribute to neurodevelopmental disorders and shows that mTOR activation can alleviate these defects.

Epigenetic Modulation to perturb the SYNGAP1 Intellectual Disability (ID) that ameliorates synaptic and behavioural deficits

This study shows that modulating histone acetylation with a small molecule activator improves synaptic and behavioural deficits in a SYNGAP1 mutation model.

Convergent Transcriptomic Evidence Reveals the Dysfunctional Quantitative Mechanism of Synaptic Plasticity Control in ASD

The paper identifies dysregulated molecular pathways in ASD by analyzing transcriptomic data and developing new computational methods to model signal transduction networks.

Autism genes converge on microtubule biology and RNA-binding proteins during excitatory neurogenesis

The paper represses 87 high-confidence ASD genes in a human cortical neurogenesis model, identifying 17 genes that disrupt developmental trajectory and reveal convergence on microtubule biology and RNA-binding proteins.

Cyfip2 controls the acoustic startle threshold through FMRP, actin polymerization, and GABAB receptor function.

This study identifies Cyfip2's role in regulating the acoustic startle threshold through FMRP, actin polymerization, and GABAB receptor function in zebrafish.

Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes

This study identifies transcriptomic changes in mouse hippocampus due to social isolation and links them to human genetic risk factors for neurodevelopmental disorders.

Expanding the phenotypic spectrum of TRAF7 syndrome: report of eleven new cases and literature review.

This paper reports eleven new TRAF7 syndrome cases, expands the phenotypic spectrum, and highlights clinical complications requiring tailored management.

Direct targets of MEF2C are enriched for genes associated with schizophrenia and cognitive function and are involved in neurogenesis and mitochondrial function

The paper identifies MEF2C direct target genes enriched for schizophrenia and cognitive function genes, showing their involvement in neurogenesis and mitochondrial function.

Systemic pharmacological suppression of neural activity reverses learning impairment in a mouse model of Fragile X syndrome

The paper shows that reducing neural activity in a Fragile X syndrome mouse model reverses learning impairments through pre-training that counteracts LTD.

Microcircuit failure in STXBP1 encephalopathy leads to hyperexcitability

This study identifies excitatory synapse dysfunction in microcircuits as the cause of hyperexcitability in Stxbp1 haploinsufficiency and shows that ampa-kines can rescue this defect.

MeCP2 Represses the Activity of Topoisomerase IIβ in Long Neuronal Genes

This study identifies a functional interaction between MeCP2 and TOP2β in neurons, showing MeCP2 inhibits TOP2β activity at long genes, which may contribute to neurodevelopmental disorders.

Molecular consequences of PQBP1 deficiency, involved in the X-linked Renpenning syndrome

This study investigates the molecular consequences of PQBP1 deficiency in Renpenning syndrome by analyzing gene expression and protein interactions, identifying dysregulated genes and a novel UPF3B isoform.

Adaptive functions correlate with evoked neurotransmitter release in SYT1-associated neurodevelopmental disorder

The paper shows that SYT1 variants impair exocytosis, correlating with neurodevelopmental symptoms, suggesting a genotype-function-phenotype relationship.

Late onset and regional heterogeneity of synaptic deficits in cortical PV interneurons of Shank3B-/- mice

This study investigates synaptic deficits in cortical PV interneurons of Shank3B-/- mice, finding reduced mEPSC frequency in adulthood but not early development, and region-specific differences.

Inhibitory synaptic transmission is impaired in the Kölliker-Fuse of male, but not female, Rett Syndrome Mice

This study shows that inhibitory synaptic transmission is impaired in male, but not female, Rett Syndrome mice in the Kölliker-Fuse region, suggesting sex-dependent mechanisms in breathing abnormalities.

FMRP phosphorylation modulates neuronal translation through YTHDF1

This study shows that FMRP phosphorylation regulates neuronal translation via YTHDF1, revealing a mechanism for FXS pathology and suggesting YTHDF1 as a therapeutic target.

Tug-of-peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 Duplication Syndrome of Autism

The paper develops a visual paradigm to study visual motion processing in a mouse model of autism and finds reduced perceptual reversals and increased local motion stability in MECP2 duplication mice.

A Massively Parallel Screen of 5'UTR Mutations Identifies Variants Impacting Translation and Protein Production in Neurodevelopmental Disorder Genes

The paper screens 5'UTR mutations in neurodevelopmental disorder genes to identify functional variants impacting translation and protein production, finding some mutations affect known syndromic autism genes in neurons.

HDAC inhibitors rescue MeCP2T158M speckles in a high content screen

The paper screens FDA-approved drugs and compounds to identify small molecules that rescue MeCP2-T158M speckle formation in NIH3T3 cells, finding HDAC inhibitors as effective rescuers.

CTCF regulates anxiety and depression like behavior and maintenance of neuronal identity in the adult mouse brain

This study shows that CTCF is essential for maintaining neuronal function and behavior in adult mice, not just during development, by affecting gene expression, morphology, and social behavior.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

This study examines how different DNMT3A mutations cause varied behavioral, epigenetic, and transcriptional issues in neurodevelopmental disorders.

Activity-Induced MeCP2 Phosphorylation Regulates Retinogeniculate Synapse Refinement

This study shows that activity-induced phosphorylation of MeCP2 is critical for retinogeniculate synapse maturation during early postnatal development.

Drosophila Bchs overexpression recapitulates human WDFY3 neurodevelopmental phenotypes with implications for glial cell involvement in altered head circumference

This study shows that overexpression of the Drosophila Bchs gene, an ortholog of human WDFY3, causes neural developmental issues in both neurons and glial cells, mirroring human neurodevelopmental disorders.

Autism candidate gene rbm-26(RBM26/27) regulates MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment.

This study identifies RBM-26 as a regulator of MALS-1 that prevents mitochondrial dysfunction and axon degeneration during neurodevelopment in C. elegans.