Genetics and Neurodevelopmental Disorders

The human-specific gene FRMPD2B couples postnatal experience to the expansion of cortical connectivity

This paper identifies the human-specific gene FRMPD2B as an activity- and experience-regulated modifier of cortical connectivity, showing its role in postnatal brain development.

HERC1 Loss of Function Causes a Developmental Disorder with Impaired Hippocampal Function

This study shows that HERC1 loss causes neurodevelopmental abnormalities in mice, including hippocampal dysfunction and sex-dependent synaptic defects.

Structural analysis of HERC2/UBE3A and HERC2/DOCK10 complexes provides new insights into the molecular basis of Angelman, Angelman-like and Dup15q Syndromes

The paper analyzes the structural and functional interactions of HERC2/UBE3A and HERC2/DOCK10 complexes to understand their role in Angelman and Dup15q Syndromes.

Imbalance between RNA-binding proteins and the WAVE regulatory complex underlies the toxic gain-of-function effects of the CYFIP2 Arg87Cys variant in neurodevelopmental disorders

A mechanistic classification of GNAO1 mutations links Gβ γ sequestration to hyperkinetic disease and treatment response

This study classifies GNAO1 mutations into functional categories and evaluates therapeutic strategies for NEDIM and DEE, finding that specific mutations are linked to hyperkinetic symptoms and that small molecules reduce hyperlocomotion.

Tilted striatofugal balance and beneficial effects of facilitating mGlu4 receptor activity in the Fmr1-/- mouse model of Fragile X Syndrome

The paper investigates D1/D2-SPN balance in FXS mice and shows that mGlu4 facilitation rescues social deficits.

STRADA Deficiency Impairs Cortical Interneuron Development in Humans and Mice

This study shows STRADA deficiency reduces cortical inhibitory interneurons and increases striatal interneurons in mice and a human PMSE brain, suggesting impaired interneuron migration contributes to the disorder.

CREBBP variants underlying Menke-Hennekam syndrome exhibit histone acetyltransferase hyperactivity with divergent phase behaviors

This study identifies two CREBBP variants causing Menke-Hennekam syndrome that increase HAT activity but disrupt phase separation differently, with HAT inhibition restoring condensate dynamics in one variant.

Cellular context defines brain-specific functions of genes associated with neurodevelopmental disorders

The paper identifies brain-specific functions of NDD-associated genes by analyzing gene expression and regulatory mechanisms across tissues.

Repetitive transcranial magnetic stimulation targeting motor cortical region induces cell-type-specific transcriptional reprogramming and behavioral recovery in non-human primate model of Rett syndrome

This study shows that rTMS targeting the motor cortex in a non-human primate model of Rett syndrome improves behavioral outcomes and induces cell-type-specific transcriptional changes.

Disrupted glial-mediated synaptic refinement in Fragile X syndrome

This study identifies impaired glial-mediated synaptic refinement in FXS model mice, showing enhanced astrocyte-microglia signaling and synaptic over-engulfment as key features.

CDKL5 deficiency alters cell subtype-specific molecular programmes and intercellular signalling in the mouse hippocampus

This study uses snRNA-seq to analyze gene expression changes in the hippocampus of CDKL5-deficient mice, identifying cell-type-specific transcriptional alterations and intercellular signaling changes.

Cortisol homeostasis and glucocorticoid signaling are altered in FMR1 full mutation and premutation carriers.

This study examines cortisol homeostasis and glucocorticoid signaling in FMR1 mutation carriers, finding altered gene expression and methylation patterns associated with CGG-repeat expansions.

Systematic Functional Interrogation of Neurodevelopmental Disorder Risk Variants

This study identifies 38 expression-modulating variants associated with neurodevelopmental disorders and links them to neurodevelopmental transcriptional programs using MPRA and CROP-seq.

Neurobehavioral Profiles and Clinical Consequences of MYT1L-Related Neurodevelopmental Disorder: Insights from the Brain Gene Registry.

This study characterizes MYT1L-Related Neurodevelopmental Disorder using data from the Brain Gene Registry, identifying cognitive, behavioral, and clinical features in affected individuals.

Distinct Patterns of Adaptive Decision-Making in Mouse Models of Neurodevelopmental Disorders

This study uses reversal learning tasks and computational modeling to identify distinct cognitive impairments in mouse models of neurodevelopmental disorders.

Haploinsufficiency, de novo and biallelic missense variants in CSMD2 are associated with neurodevelopmental disorders

The paper identifies rare variants in CSMD2 associated with neurodevelopmental disorders, showing both recessive and dominant inheritance patterns and functional impairments.

Human-specific CCG-repeat insertion in the RBFOX1 promoter implicated in autism and speech enhances EGR1-responsive activity

A human-specific CCG insertion in the RBFOX1 promoter boosts EGR1-driven reporter activity in HEK293T cells, as does an autism-linked CCG-gaining duplication in PTCHD1.

FMR1 Perturbations Disrupt Sensory Corticostriatal Circuits and Mitochondrial Energetics in Fragile X Syndrome

This study shows that FMR1 perturbations disrupt sensory corticostriatal circuits and mitochondrial function in FXS, with interventions improving social and cognitive deficits.

Dose dependent impact of global Cc2d1a reduction on cognitive, social, and metabolic phenotypes

This study investigates the dose-dependent effects of CC2D1A reduction in mice, finding that ~90% loss leads to ASD/ID-like behaviors in males and metabolic changes, while ~80% loss does not.

PTEN Subcellular Localization Dictates Function

Nuclear-excluded PTEN rescued all knockout overgrowth phenotypes in mouse dentate granule neurons; nuclear-restricted PTEN rescued only spine head area and partly soma size, so localization shapes function.

Disease-associated variants alter a novel physiological role of hnRNP H2 in neuronal development

This study identifies hnRNP H2's role in neuronal development and shows how disease variants disrupt its function, leading to neurodevelopmental defects.

Dysregulation of cAMP-PKA-mediated mechanisms disrupts basal synaptic function in the absence of presynaptic FMRP

This study shows that presynaptic FMRP is required for efficient basal neurotransmission at hippocampal mossy fiber synapses through cAMP-PKA signaling.

Integrative genetic and transcriptomic analysis identifies candidate genes and compounds for Fragile X syndrome and autism spectrum disorder

Developmental Convergence Across Diverse Genetic Architectures in Childhood Apraxia of Speech

The paper identifies multiple genetic variants associated with childhood apraxia of speech through whole-exome sequencing and functional analysis, proposing four novel candidate genes.

A massively parallel reporter assay of MECP2 cis-regulatory elements reveals genetic candidates for male-biased autism

The paper identifies noncoding MECP2 variants that cause male-biased autism by disrupting CRE activity and reducing MECP2 expression.

Novel Co-expression of Group I Metabotropic Glutamate Receptor During Mouse Cochlear Nucleus Development

The paper examines mGluR expression in mouse cochlear nucleus during development, finding mGluR5 is more abundant early and mGluR1 dominates later, with no significant effect of Fmr1 genotype on expression patterns.

Recessive loss-of-function and dominant gain-of-function variants in FBXO31 are associated with distinct neurodevelopmental disorders

The paper identifies two distinct FBXO31 variants causing different neurodevelopmental disorders: a dominant gain-of-function variant and a recessive loss-of-function deletion.

Dysregulation of FMR1 Splicing in Human Fragile X Syndrome

This study identifies FMR1-217 mis-splicing in FXS as a result of CGG repeat expansion, R-loop formation, and impaired Pol II elongation, with potential therapeutic rescue via splice-switching ASOs.

Precocious maturation and Purkinje cell dysfunction in the mouse Chd8 haploinsufficient cerebellum

This study examines the effects of Chd8 haploinsufficiency on cerebellar development and function in mice, revealing cell-type-specific transcriptomic and physiological changes.