Genetics and Neurodevelopmental Disorders

Pleiotropy of autism-associated chromatin regulators

The paper investigates the role of chromatin regulators in autism spectrum disorder (ASD) by examining their involvement in microtubule biology and cellular proliferation, finding that ASD risk genes affect these processes and are enriched among microtubule-associated proteins.

Biallelic loss of function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental delay syndrome

This study identifies biallelic loss-of-function variants in WBP4 as a cause of a neurodevelopmental syndrome with variable manifestations.

KAT6A mutations drive transcriptional dysregulation of cell cycle and Autism risk genes in an Arboleda-Tham Syndrome cerebral organoid model

This study shows KAT6A mutations cause transcriptional dysregulation of cell cycle and autism risk genes in cerebral organoids, leading to delayed neural differentiation and altered gene expression patterns.

A de novo missense variant in EZH1 associated with developmental delay exhibits functional deficits in Drosophila melanogaster

A de novo EZH1 variant p.Ala678Gly is linked to neurodevelopmental delay and shows functional deficits in Drosophila melanogaster.

Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder

The paper reports a cohort of 35 individuals with CUL3 variants causing a syndromic neurodevelopmental disorder, showing loss-of-function variants disrupt protein homeostasis by impairing proteasomal degradation of CUL3 substrates.

BrainRBPedia: a resource for RNA-binding proteins relevant to neurodevelopmental disorders

BrainRBPedia is a database of 1072 RNA-binding proteins linked to neurodevelopmental disorders, with a machine learning model prioritizing RBPs for autism and intellectual disability.

Strain-dependent effects on neurobehavioral and seizure phenotypes in Scn2aK1422E mice

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.

The autism-associated loss of δ-catenin functions disrupts social behaviors

This paper investigates how the G34S mutation in δ-catenin causes loss of function leading to social dysfunction in ASD by altering glutamatergic activity and GSK3β-mediated degradation.

A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects

This paper introduces a knock-in mouse model of ATR-X syndrome carrying a common patient mutation, showing craniofacial defects, microcephaly, and impaired neurological function.

Inactivation of DRG1, encoding a translation factor GTPase, causes a Recessive Neurodevelopmental Disorder

This study identifies rare DRG1 variants causing a recessive neurodevelopmental disorder and shows their functional impact on GTPase activity and protein stability.

CTCF barrier breaking by ZFP661 promotes protocadherin diversity in mammalian brains

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

ARID1B controls transcriptional programs of axon projection in the human corpus callosum

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.

A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 as a significant cause of intellectual disability

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.

Drosophila FMRP recruits the miRISC to target mRNAs to repress translation

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

Learning about neurodiversity from parents - auditory gestalt perception of prelinguistic vocalisations

This study examines how parents of children with Rett syndrome perceive prelinguistic vocalizations, finding they can distinguish RTT vocalizations from typically developing ones, even when the RTT vocalizations are considered inconspicuous by experts.

Investigating the role of common cis-regulatory variants in modifying penetrance of putatively damaging, inherited variants in severe neurodevelopmental disorders

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.

Prospective phenotyping of CHAMP1 disorder indicates that coding mutations do not act through haploinsufficiency

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.

Genetic and Genomic Analyses of Drosophila melanogaster Models of Chromatin Modification Disorders

This study uses Drosophila models to analyze gene expression and behavior changes in chromatin modification disorders, identifying co-regulated genes and potential therapeutic targets.

Wild-type MECP2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome

The paper identifies age-dependent changes in MECP2 expression and associated behavioral and cellular phenotypes in a female mouse model of Rett syndrome.

Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models

The paper investigates how mRNA half-life buffers transcription rate changes in Rett syndrome models, identifying post-transcriptional mechanisms in human and mouse neurons.

Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

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.

Activation of the CA2-vCA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice

This study shows that activating the CA2-vCA1 pathway in Shank3B knockout mice restores social recognition function, suggesting potential therapeutic targets for social memory deficits.

Phosphorylation alters FMRP granules and determines their transport or protein synthesis abilities

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

The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons

This study investigates the role of UBE3A in Dup15q syndrome using CRISPR-corrected patient-derived neurons, showing UBE3A overexpression is necessary for most neuronal deficits but not synaptic phenotypes.

Human synaptic neoteny requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition

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

Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease

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

Mecp2 deletion results in profound alterations of developmental and adult functional connectivity

This study examines functional connectivity changes in Mecp2 knockout mice, finding disrupted connectivity in males and subtle changes in females, suggesting sex-specific roles of MeCP2 in circuit development.

MeCP2 regulates Gdf11, a dosage-sensitive gene critical for neurological function

This study identifies Gdf11 as a MeCP2-regulated gene critical for neurological function, showing that altering its dosage affects behavior and longevity in mouse models.

Epilepsy-related CDKL5 deficiency slows synaptic vesicle endocytosis in central nerve terminals

This study shows that CDKL5 deficiency impairs synaptic vesicle endocytosis in neurons, highlighting its presynaptic role in epilepsy.

Mecp2 knock-out astrocytes affect synaptogenesis by IL-6 dependent mechanisms

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