Genetics and Neurodevelopmental Disorders

Expanding clinical and variant spectrum of CBX1-related syndrome: Report of three novel cases

This paper reports three novel de novo CBX1 variants in patients with developmental delay and describes genotype-phenotype correlations.

An automated machine vision-based index for Rett Syndrome provides a generalizable framework for modeling rare disease therapeutics

This paper develops an automated machine vision-based index for Rett Syndrome that improves preclinical phenotyping by detecting disease-relevant behaviors and reducing animal use.

The Female Side of Autism: Sexual Dichotomies impacting the Helsmoortel-Van der Aa syndrome pathology.

This study investigates how biological sex influences the behavioural, molecular, and therapeutic responses in a mouse model of Helsmoortel-Van der Aa syndrome, finding sex-dependent differences in molecular pathways and treatment response.

Loss of SEZ6L2 disrupts synaptic architecture and drives progressive behavioral deficits

This study characterizes Sez6l2 knockout mice, showing behavioral and synaptic deficits, and compares them to Sez6 triple knockout mice, highlighting SEZ6L2's non-redundant role in brain function.

An ASXL3-thyroid hormone axis in parvalbumin interneurons controls autism-like behaviors

This study identifies an ASXL3-thyroid hormone axis in parvalbumin interneurons that regulates autism-like behaviors and shows that early TH supplementation can reverse these effects in mice.

KMT2E recruitment by H3 serotonylation regulates neurodevelopmental chromatin dynamics

This study identifies KMT2E as a reader of H3K4me3Q5ser, showing its role in regulating chromatin dynamics and neurodevelopmental gene expression in ODLURO syndrome.

Chemical genetic screen for substrates of autism risk gene NUAK1 uncovers its role in ARF6 mediated dendritic spine maturation

This study identifies NUAK1 substrates in neurons and shows that NUAK1 phosphorylation of PSD3 regulates ARF6 activation and dendritic spine maturation, linking NUAK1 to autism risk.

Convergent and divergent phenotypic impacts of estradiol on neurodevelopmental disorder risk genes

The paper evaluates estradiol's effects on ASD/NDD genes using human neurons and zebrafish, finding both convergent transcriptomic effects and gene-specific cellular and behavioral rescue.

Developmental Cerebellar Pathology in Mouse Models of SCN2A Premature Termination Codon Variants

This study examines cerebellar development in mouse models with SCN2A premature termination codon variants, finding age- and position-dependent effects on cerebellar structure and function.

Compromised striatal structure and function in mouse models of RARB-related disorder

This study investigates RARB-RD mouse models and finds that both GOF and DN variants compromise striatal structure and function, with transcriptional effects more severe than a null allele.

DE NOVO VARIANTS IN THE POLY(RC)-BINDING PROTEIN GENE PCBP1 CAUSE A NEURODEVELOPMENTAL DISORDER

The paper identifies de novo variants in PCBP1 causing neurodevelopmental disorders, showing impaired dendritic arborization and increased exon skipping in T cells.

Characterization of the Grin1Q536R/+ mouse: a preclinical model for GRIN1-related neurodevelopmental disorder

The paper characterizes a Grin1Q536R/+ mouse model carrying a GRIN1 variant, showing age- and sex-dependent behavioral and physiological changes linked to GRIN1-NDD.

Structures of MeCP2 bound to nucleosomes reveal distinct mechanisms of Rett syndrome mutations

This study determines cryo-EM structures of MeCP2 bound to nucleosomes and identifies how RTT mutations affect nucleosome interactions and chromatin targeting.

Fragile X syndrome-linked mutations impair FMRP accumulation in neuronal transport granules

This study shows that specific FMRP mutations impair its accumulation in RNA granules, suggesting a role for these domains in granule assembly and potential involvement in FXS pathogenesis.

Altered stimulus-specific adaptation at the auditory cortex of a mouse model of Fragile X Syndrome

This study examines stimulus-specific adaptation in the auditory cortex of FMR1-KO mice, finding reduced adaptation in male KO mice compared to WT and female KO mice.

Reduction of forebrain interneurons alters cellular organization and cortical neurogenesis in a mouse model of X-linked intellectual disability

This study investigates the effects of Arx removal in MGE-derived interneurons in mice, revealing altered cellular organization and cortical neurogenesis in both male and female models of X-linked intellectual disability.

A conserved transcriptional axis links cortical organization, developmental timing and autism-associated perturbations

The paper identifies a conserved transcriptional axis in human and mouse cortex linking developmental timing, cortical organization, and autism-associated mutations.

CHD8 orchestrates chromatin landscapes during early female neuronal differentiation

This study investigates CHD8's role in female neuronal differentiation using multi-omics analysis, revealing its impact on chromatin structure and gene regulation in mouse models.

A patient derived missense mouse model of Kabuki syndrome 1

The paper introduces a missense mouse model of Kabuki syndrome with intact KMT2D function, showing similar phenotypes to loss-of-function models but without altered adult neurogenesis and with novel kidney agenesis.

Large-Scale EHR-Based Phenotyping of an FMR1 Premutation Cohort at a Referral Hospital

This study uses EHR data to characterize FMR1 premutation carriers, identifying common diagnoses before mutation confirmation and highlighting diagnostic delays.

MECP2 MBD-ID Module: A Unified DNA/RNA Binding Interface Disrupted in Rett Syndrome

This paper identifies the MBD-ID module as a unified DNA/RNA binding interface in MECP2, showing it is disrupted in Rett syndrome due to mutations in the intervening domain.

Complementary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome

The paper develops murine and zebrafish Wac deletion models to study DeSanto-Shinawi Syndrome, finding craniofacial, behavioral, and neurodevelopmental phenotypes similar to the human condition.

Loss of FMRP leads to translationally relevant functional connectivity differences in a rat model of Fragile X Syndrome

The paper investigates how loss of FMRP in a rat model of FXS affects functional connectivity over development and whether early lovastatin treatment can normalize it.

Androgens mediate sexual dimorphism in Pilarowski-Bjornsson Syndrome

The paper investigates sex-specific penetrance in PILBOS, showing male overrepresentation and androgen-mediated sexual dimorphism through genetic and mouse model studies.

Autism-associated SCN2A deficiency disrupts cortico-striatal circuitry in human brain assembloids

This study shows that SCN2A deficiency in human brain assembloids disrupts cortico-striatal circuitry by impairing axonal projections and synaptic transmission, leading to hyperexcitability.

Molecular and functional profiling distinguishes PACS1 syndrome variant from PACS1 loss-of-function in iNeurons

The paper compares the molecular and functional effects of a PACS1 variant (p.R203W) with complete PACS1 loss-of-function in iPSC-derived neurons, finding distinct phenotypes suggesting a non-loss-of-function mechanism.

Metabolic collapse as a mechanism of developmental regression: convergent evidence from Kleefstra syndrome FDG-PET/CT imaging and Drosophila modelling

This study links metabolic vulnerability and sleep disturbances in Kleefstra syndrome using FDG-PET/CT imaging and Drosophila models.

The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs

This study identifies BAF complex interaction with FOS in regulating ASD-associated gene programs through enhancer activation and shows how genetic variants disrupt this process.

Cognitive and Synaptic Impairment Induced by Deficiency of Autism Risk Gene Smarcc2 and its Rescue by Histone Deacetylase Inhibition

This study shows that Smarcc2 deficiency causes cognitive and synaptic impairments in mice, which can be rescued by HDAC inhibition.

Impaired formation and updating of internal predictive models in a rat model of Fragile X Syndrome

This study uses a probabilistic oddball task to show that Fmr1 KO rats have impaired predictive processing, failing to adapt to changing statistics and overweighting immediate sensory input.