Genetics and Neurodevelopmental Disorders

The paper identifies CHD8 interactions in mouse brain, revealing a role in chromatin-associated RNA processing and highlighting dosage sensitivity in neurodevelopmental disorders.

The paper introduces Endo-GeneScreen, a platform that identifies small molecules regulating endogenous protein levels, and demonstrates its application in finding probes for Syngap1-related neurodevelopmental disorder.

This study creates an age-aware genotype-phenotype atlas for 87 neurodevelopmental disorders using data from the Simons Searchlight cohort, identifying gene-specific risk profiles and age-dependent penetrance patterns.

This study describes the age-related clinical and neuroimaging features of SYT1-associated neurodevelopmental disorder in 39 individuals with de novo variants.

This study shows that reactivating the silenced X chromosome in heterozygous Nexmif-deficient mice improves neuronal and behavioral deficits using pharmacological and CRISPRa approaches.

This study identifies the developmental origin of seizures in Lowe syndrome by showing that docrl in neural stem cells during embryonic neurogenesis is required to prevent heat-induced seizures in Drosophila.

This study identifies MeCP2's interaction with the super elongation complex and shows it regulates transcription by modulating RNA polymerase II binding and gene expression.

This study shows that FMRP acutely regulates neuronal plasticity in adult Drosophila neurons by modulating sif mRNA translation and Rac1 activity.

This study shows that reduced CB1 receptor function in GABAergic neurons of FXS model mice rescues cortical hyperexcitability and sensory-driven synchrony deficits.

This study shows that SHANK2 variants cause hypersynchronous neuronal network activity in human iPSC-derived neurons, which is rescued by mGluR5 agonism.

This study identifies a role for Shank3 in regulating affective empathy through cortico-amygdala circuits in a mouse model of autism.

This study shows that reducing Shank3 in the nucleus accumbens decreases social motivation in mice without affecting food reward or anxiety.

The paper investigates altered neuronal activity in the mPFC of Mecp2 knockout mice during social interactions, linking it to social memory impairments.

The paper investigates the missense mutation ADNP p.C687R in HVDAS, showing it disrupts chromatin regulation and GABAergic differentiation through gain-of-function mechanisms.

The paper uses AlphaFold to model AnkB interactions with NrCAM and β2-Spectrin, identifies critical residues, and shows how ASD mutations disrupt these interactions and neuronal function.

This study shows that ZMYND11 inhibits KMT2A to regulate neuronal development, and a mutation in ZMYND11 disrupts this interaction, leading to developmental and behavioral abnormalities.

The paper investigates the reciprocal regulation of the H3 histamine receptor in Rett syndrome and MECP2 Duplication syndrome, showing reduced H3 receptor expression in RTT and increased in MDS, and evaluates potential therapeutic effects of agonist and inverse agonist drugs.

The paper shows TET3 and MECP2 interact to regulate neuronal maturation, with TET3 critical for functional development and MECP2 inhibiting TET3 activity.

This study functionally characterizes SATB2 missense variants to identify distinct effects on chromatin binding and transcriptional activity, revealing partial loss-of-function and some variants with increased function.

The paper identifies non-CGG trinucleotide repeat mutations in the FMR1 gene associated with Fragile X Syndrome phenotypes, suggesting broader genetic screening is needed beyond CGG repeats.

This study shows that reduced BRD1 function in minipigs leads to coordinated neurodevelopmental and metabolic changes in both brain and peripheral tissues.

This study shows that FMRP depletion in human neurons causes cyclic-AMP-dependent hyperexcitability, which can be corrected by inhibiting phosphodiesterase 4D.

The paper generates a mouse model with a deletion in an enhancer of EBF3, showing reduced Ebf3 expression and sex-specific behavioral and phenotypic differences.

This study evaluates gap-induced prepulse inhibition and habituation in FMR1-KO mice during early development, finding sex differences and developmental changes in auditory responses.

This study identifies SEMA3C as an astrocyte-secreted protein contributing to Rett Syndrome pathology and shows its normalization rescues dendritic and behavioral deficits.

This study investigates the role of ZMYND11 in neurodevelopment by analyzing its effects on cortical neural stem cells and splicing regulation in ASD risk factors.

This study uses long-read sequencing to reveal extensive somatic mosaicism in FMR1 repeats and methylation in FXTAS brain tissue, identifying expansions and contractions beyond traditional methods' resolution.

This study identifies AUTS2's dual DNA/RNA binding in human neural progenitors and shows its role in regulating Wnt pathway genes, linking its disruption to neurodevelopmental disorders.

This study shows that inhibiting miR132-3p with ASOs increases MECP2 mRNA in SH-SY5Y cells, suggesting a potential therapeutic approach for Rett syndrome.

This study characterizes a mouse model with a GluN2B protein-truncating variant, showing reduced NMDAR function and moderate behavioral effects.