1. Caux A, Jobic F, Keren B, Billes A, Magry V, L’Haridon A, Darwiche W, Jedraszak G, Morin G. Case report and literature review of neurodevelopmental syndrome linked to DOT1L variants. Gene. 2026; 983: 149987.

INTRODUCTION: The DOT1L gene encodes a histone lysine methyltransferase that has the distinctive characteristic of being composed of a DOT1 catalytic domain that targets lysine 79 of the core globular domain of histone H3. DOT1L missense variants have recently been implicated in an autosomal dominant inheritance syndrome with developmental delay and congenital anomalies in postnatal cohorts. We report the twenty-sixth patient with this disorder. METHODS: Trio genome sequencing (GS) was performed in a patient with developmental delay. RESULTS: Clinical examination showed a predominant global developmental delay affecting language, with cerebral abnormalities visible on magnetic resonance imaging, hypotonia, and ophthalmological and musculoskeletal abnormalities. GS revealed a de novo heterozygous missense variant in exon 3 of DOT1L (c.161C > T; p.(Ala54Val)), which is reported for the first time as the cause of developmental delay and congenital anomalies. DISCUSSION: Among the 26 reported patients, 23 have missense variants, two have truncating variants, and one has an in-frame deletion. The mode of transmission is predominantly de novo. Current studies indicate multiple pathogenic mechanisms underlying DOT1L-related disorder, including both gain-of-function and loss-of-function effects, underscoring the complexity of the disease etiology. Although the gene exhibits intolerance to loss-of-function variants, a considerable number of truncating variants are observed in control populations, suggesting incomplete penetrance and heterogeneity in the phenotypic expression of DOT1L-associated disorder. No phenotype-genotype correlation could be established. Among reported patients, including ours, the most consistent clinical manifestations are global developmental delay, predominantly affecting language and behavior, and possibly distinctive facial features.

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2. Dey S, Das A. Genetics of Autism Spectrum Disorder underscores the role of altered spontaneous neuronal activity as a catalyst for the neurodevelopmental anomalies. Brain Res. 2026; 1875: 150164.

Autism Spectrum Disorder (ASD) represents a diverse set of neurodevelopmental disorders diagnosed in children exhibiting common behavioral impairments in social communication and excessive repetitive behaviors. Genetic approaches and large-scale genomic studies have uncovered hundreds of ASD-associated genes with diverse molecular functions contributing to various biochemical and physiological pathways. Despite the underlying genetic diversity, the convergence of phenotypic features suggests the disruption in shared neurobiological mechanisms contributing to ASD. Spontaneous neuronal activity (SNA), the stimulus-independent firing of neurons, which is observed even during neuronal development, has been known to be crucial for neural circuit maturation. Functional neuroimaging studies have demonstrated that SNA is a central process disrupted in ASD patients and mutation-based animal and cellular models. SNA orchestrates critical developmental programs during neuronal maturation such as dendritic arborization, synaptic pruning, excitatory-inhibitory balance, and activity-dependent transcriptional regulation. Perturbations in these dynamics may provide a unifying mechanistic framework linking genetic mutations to abnormal circuit formation and behavioral anomalies. In this review, we collate the genetic and genomic studies to evaluate the contribution of ASD genes in regulating the spontaneous firing of neurons. We classify ASD genes into generators, sensors, transducers, and responders of activity-induced signals and discuss their roles in regulating membrane excitability, transducing the signal to cytoplasmic or nuclear targets to transform the neuronal gene expression program, eventually impacting neuronal and synaptic development. We attempt to substantiate the contribution of altered SNA as the single major common neurological mediator connecting genetic mutations with the common behavioral irregularities manifested in ASD.

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3. Han W, Yang X, Li X, Wang J, Liu J, Pang W. Machine learning-based diagnosis of autism spectrum disorder in children and adolescents using eye-tracking data: a systematic review and meta-analysis. Int J Med Inform. 2026; 208: 106235.

OBJECTIVE: Eye-tracking technology has been increasingly investigated as an objective approach for distinguishing individuals with Autism Spectrum Disorder (ASD) from typically developing (TD) individuals. Artificial intelligence and machine learning (ML) methods have been widely applied to support ASD diagnosis and treatment, and prior studies suggest that ML models leveraging eye-tracking data can achieve high diagnostic accuracy. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of machine-learning models using eye-tracking data to distinguish children and adolescents with ASD from TD peers. METHODS: We systematically searched PubMed, Embase, Web of Science, IEEE Xplore, Scopus, and the Cochrane Library from inception to August 3, 2025. We included studies that applied ML methods to eye-tracking data to distinguish children with ASD from TD children. We extracted data on participant characteristics, model performance, eye-tracking protocols, and machine-learning algorithms. The review protocol was registered in PROSPERO (CRD420251162462). RESULTS: We identified 1,045 records, of which 25 studies were included in the meta-analysis. The included studies comprised 2,319 participants, with sample sizes ranging from 32 to 529 per study. The pooled accuracy, sensitivity, and specificity of machine-learning models using eye-tracking data to distinguish children with ASD from TD children were 85 % (95 % CI, 81-89 %), 86 % (95 % CI, 82-89 %), and 86 % (95 % CI, 79-91 %), respectively. These results suggest that eye-tracking-based machine-learning approaches have good diagnostic performance for identifying ASD. CONCLUSION: Eye-tracking-based machine-learning approaches show considerable potential for distinguishing children with ASD from TD children. However, the robustness and generalizability of these findings are limited by the lack of external validation, small sample sizes, and substantial between-study heterogeneity. To establish generalizability, future research should prioritize standardized eye-tracking paradigms and large-scale, prospective, multicenter study designs with external validation. Such efforts may facilitate the translation of these models into clinical practice as objective and efficient adjunctive screening tools.

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4. Song S, Wei Q, Tu Y, Zhou S, Zhou J, Tao J, Chen Y, Zhou H, You M. Chlorpyrifos-induced autism and depression-like behaviors are ameliorated by trehalose: Integrating network pharmacology and toxicology analyses and animal experiments. Environ Pollut. 2026; 393: 127670.

The risk of autism spectrum disorder (ASD) is elevated by exposure to the organophosphate pesticide chlorpyrifos (CPF) during pregnancy and lactation. As a neurodevelopmental disorder, ASD often co-occurs with depression, exacerbating the social isolation experienced by affected individuals. Trehalose (Tre), a naturally occurring non-reducing sugar, has neuroprotective properties. Nevertheless, the mechanisms by which it exerts protective effects against CPF-induced ASD and depression-like behaviors remain unclear. The objective of study was to investigate the mechanisms underlying Tre combating CPF-induced ASD and depression through network pharmacology and toxicology analyses. In animal studies, Tre was administered to offspring mice exposed to CPF during pregnancy and lactation. Behavioral assessments revealed that Tre alleviated CPF-induced repetitive and stereotypic behaviors, social deficits, and depression-like behaviors in offspring mice. Findings from network pharmacology and toxicology analyses and animal experiments supported the notion that mammalian target of rapamycin-related autophagy and TLR4-related necroptosis signaling may contribute to the protective effects of Tre against CPF-induced hippocampal damage. This research offers valuable information regarding the potential protective effects of Tre against neurodevelopmental disorders linked to environmental chemicals.

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5. Stokke Jensen S, Midya V, Arora M, Eek Brandlistuen R, Havdahl A, Dehli Andersen G, Klock KS. Pre- and postnatal trace element levels in primary teeth of children with and without an autism spectrum diagnosis. Environ Res. 2026; 295: 124001.

BACKGROUND: The global prevalence of autism spectrum diagnosis (ASD) is increasing. Fetal and early-life exposure to trace elements has been associated with increased likelihood of ASD, but evidence regarding timing of exposure remains limited. AIM: This study investigates prenatal and early-life exposure to non-essential and essential elements, individually and as mixtures, in children with and without ASD, stratified by child sex. METHODS: The sample included 170 children from the Norwegian Mother, Father and Child Cohort Study (MoBa), of whom 75 were clinically diagnosed with ASD and 95 were not. Elemental levels were measured in primary tooth dentine using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to investigate case-control differences in levels of pre-and postnatal non-essential and essential elements as well as their mixtures. RESULTS: Significant differences in lead (Pb) levels were observed between ASD case and control groups: The ASD male group had lower Pb levels from 15 to 11 weeks prenatally, while ASD female group had lower levels from birth to 4 weeks postnatally, compared to controls. Males with ASD had higher prenatal magnesium (Mg) and lower postnatal Mg levels, as well as lower prenatal lithium (Li) levels and higher postnatal Li levels compared to controls. Additionally, males with ASD had higher prenatal and lower postnatal essential element mixture levels than controls. DISCUSSION: These findings suggest that there may be differential patterns of exposure to non-essential and essential element levels during specific developmental windows in fetal and early postnatal life in children with and without ASD.

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6. Wang B, Ahmed A, Murari K, Cheng N. Alterations in electroencephalography signals in female fragile X syndrome mouse model on a C57BL/6J background. Physiol Behav. 2026; 306: 115217.

Fragile X Syndrome (FXS), the most common monogenic cause of autism spectrum disorder, exhibits sex differences in prevalence and phenotypic severity. Electroencephalography provides translational insights into its pathophysiology, yet prior research focuses predominantly on males. In C57BL/6J mice, male Fmr1 knockout models show increased absolute gamma power across developmental stages, while female phenotypes, particularly in juveniles, remain uncharacterized. This study addresses this gap by comparing juvenile female Fmr1 knockout and wild-type mice. Frontal-parietal differential electroencephalography was recorded in home cage, light-dark test, and open field test. Analyses included absolute/relative power, peak alpha frequency, theta-beta ratio, phase-amplitude coupling, amplitude-amplitude coupling, and multiscale entropy. Knockout mice exhibited reduced absolute theta, alpha, and beta power across all conditions. Relative power analysis revealed decreased alpha and increased gamma activity. Phase-amplitude coupling showed diminished alpha-gamma coordination, while amplitude-amplitude coupling displayed state-dependent alterations. Peak alpha frequency and theta-beta ratio were reduced or unchanged depending on condition. Signal complexity remained comparable between genotypes. Behaviorally, knockout mice demonstrated hyper-exploration in the open field test. No robust correlations emerged between electroencephalography power and behavior. Our results demonstrate that juvenile female Fmr1 KO mice on a B6 background exhibit EEG alterations highly consistent with those reported in FXS patients, particularly increased gamma and reduced alpha power. The increase in gamma activity represents a conserved biomarker of potential cortical hyperexcitability, while alpha power reductions and decreased peak alpha frequency implicate thalamocortical network involvement. Together, these findings highlight the translational value of this model for studying core circuit dysfunctions in FXS.

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