1. Atalay S, Çapan Ö Y. Comprehensive in Silico Reclassification of MECP2 Variants of Uncertain Significance in Rett Syndrome: Performance Evaluation and Structural Analysis. J Mol Neurosci. 2025; 75(4): 125.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by missense variants in the MECP2 gene. However, the presence of variants of uncertain significance (VUS) poses major challenges for clinical diagnosis and genetic counseling. In this study, we systematically evaluated the performance of 33 in silico prediction tools using a curated ClinVar dataset of MECP2 missense variants. Performance metrics included accuracy, sensitivity, specificity, area under the curve (AUC), and Matthews correlation coefficient (MCC), incorporating gene-specific pathogenicity thresholds to enhance predictive precision. Evolutionary conservation was assessed using ConSurf, while structural consequences were examined using UniProt, HOPE, DUET, PyMOL, and RING. Nine top-performing tools-MutPred, MetaRNN, REVEL, MutScore, SNPred, BayesDel, ClinPred, AlphaMissense, and DeepSAV-achieved accuracies exceeding 91% and correctly classified all 19 functionally validated pathogenic variants. These tools consistently predicted 15 VUS as pathogenic, with 14 located within the methyl-CpG-binding domain (MBD) and one within the NCOR2/SMRT interaction region; all occurred at highly conserved residues (ConSurf score: 9). Structural analyses revealed destabilizing effects through altered hydrophobicity, electrostatic charge, and residue interactions, implicating impaired DNA binding or disrupted co-repressor interactions. This integrative framework, combining high-performance computational prediction with structural modeling, offers a robust approach to reclassifying MECP2 VUS and supports improved diagnostic accuracy and personalized care in RTT.

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2. Fekih-Romdhane F, Sakr F, Alhuwailah A, Chaibi LS, Helmy M, Shuwiekh HAM, Boudouda NE, Zarrouq B, Naser AY, Jebreen K, Roubi ML, Hassan BAR, Merdad N, Amin R, Nawajah I, Mohammed AH, Farhan SS, AlAni OA, Cheour M, Dabbous M, Malaeb D, Obeid S, Hallit S. Validation of the abridged version of the autism-spectrum quotient (AQ-28) in the Arabic-speaking adult general population. J Public Health Res. 2025; 14(3): 22799036251377610.

BACKGROUND: The field of autism research in adults has not yet emerged in Arab countries, which is in part due to the lack of valid, reliable autism measures. The objectives of this study were to assess the psychometric properties of the abridged version of the autism-spectrum quotient (AQ-28) in a sample of non-clinical Arabic-speaking adults. METHODS: A cross-sectional web-based study was carried-out from February to April 2024. Adults aged over 18 years from the general population of Lebanon (N = 1076, mean age of 27.90 ± 11.81 years, 63.8% females) were recruited using the snowball sampling technique. The AQ-28 was administered to participants, along with the relationship Questionnaire, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, and the Jong-Gierveld Loneliness Scale. RESULTS: The original five-factor model of the AQ-28 had good fit to the data: RMSEA = 0.061 (90% CI: 0.059-0.064), SRMR = 0.060, CFI = 0.848, TLI = 0.831, and an excellent internal consistency (Cronbach’s α = 0.91). Measurement invariance has been established across sex. Mean sum scores observed in male participants were significantly higher than those displayed by females. Autistic traits as measured by the Arabic AQ-28 correlated positively with loneliness (r = 0.16; p < 0.001), depression (r = 0.17; p < 0.001) and anxiety (r = 0.15; p < 0.001). CONCLUSION: Findings suggest that Arabic-language version of the AQ-28 provided by this study is valid, reliable, and suitable for use among Arabic-speaking adults to measure core trait dimensions of autism and screen for autism spectrum disorder. It is our hope that the new scale will generate interest among researchers in the yet unexplored field of autism research in Arab countries.

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3. Greenberg E, Joshi G, Geller D. Autism Spectrum Disorder and Obsessive-Compulsive Disorder: A Conundrum. J Am Acad Child Adolesc Psychiatry. 2025.

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4. Orr N, Shaw L, Briscoe S, Lawal HM, Martin-Pintado C, Turner M, Thompson Coon J, Garside R, Melendez-Torres GJ. The effectiveness, cost-effectiveness and experiences of interventions to reduce suicidality for autistic people: A scoping review. Autism. 2025: 13623613251376208.

Autistic people and people with elevated autistic traits are at a higher risk of suicidality (suicidal ideation, suicide plans, suicide attempts) than the general population, with over a third of autistic and possibly autistic people experiencing suicidal ideation, suicidal attempts and/or behaviour. The high prevalence of suicidality has been associated with lack of support and interventions to meet the specific needs of autistic people. This scoping review aimed to better understand the quantity and nature of existing primary research evaluating interventions to support autistic people experiencing suicidality, to inform the commissioning of future primary research. Twenty-seven studies were included: 18 focused on evaluating or developing interventions to reduce suicidality, and nine on evaluating/developing screening procedures to identify autistic people potentially at risk of dying by suicide. Findings suggest researchers are adapting and testing interventions to reduce suicidality in partnership with autistic people, but there is still work needed to enable autistic people to communicate suicidal thoughts and behaviours and develop clinician knowledge and understanding. While the number of completed studies using robust methods such as randomised controlled trials was small, this review indicates a nascent body of research evidence on interventions to reduce suicidality in the autistic population.Lay abstractAutistic, or potentially autistic, people are at higher risk of experiencing suicidality than the general population. This has been linked to a lack of support and treatments that meet the specific needs of autistic people. This scoping review brings together research developing or evaluating strategies that aim to reduce the risk of autistic people dying by suicide. We reviewed 27 studies and found that there is a small but growing number of research projects that involve autistic people to develop treatments to reduce suicidality. For example, we found a study that has adapted and tested safety planning for autistic people. Other research has been testing tools that identify and assess suicidality and understanding healthcare professionals’ perspectives on assessing suicidality. More work is needed to develop training for professionals and on adapting assessment tools so that autistic people find it easier to talk about suicidal thoughts. Future research should also aim to be inclusive of the autistic population and ensure gender and cultural diversity in those that participate in research projects. Larger trials will be needed in the future to investigate the effectiveness of treatments for autistic people and build on existing evidence.

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5. Salem SM, Ismaiel NN, Metwally AM, Ashaat EA, Kobesiy MM. miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder. J Mol Neurosci. 2025; 75(4): 124.

One of the well-studied epigenetic regulators is miRNA (miRNA) which plays critical roles in gene regulation and has been implicated in autism spectrum disorder (ASD) pathology, particularly through their involvement in neuroinflammation and neuronal regulation. MiR-146A and miR-146B are of special interest due to their dysregulation in ASD. Epigenetic modifications, such as promoter methylation, and genetic variations in miRNAs can influence their expression and function, yet their roles in ASD remain unclear. This study aimed to investigate promoter methylation patterns and sequence variations in miR-146A and miR-146B to evaluate their potential contributions to ASD. The study included Egyptian patients with ASD (ages 5-16 years) diagnosed using DSM-V criteria and assessed for severity using the Childhood Autism Rating Scale (CARS). DNA was extracted from peripheral blood samples of 93 autistic patients and 44 age-matched controls. Methylation-specific PCR (MSP) was used to analyze promoter methylation of miR-146A and miR-146B, while Sanger sequencing was employed to detect sequence variations in these genes and their flanking regions. Statistical analyses included independent t-tests, ANOVA, ROC curve, and Pearson correlation. No significant differences in promoter methylation levels of miR-146A and miR-146B were observed between ASD cases and controls or among severity subgroups (P > 0.05). Sequence variation analysis identified no significant differences in the distribution of common SNPs (rs2910164 and rs2224374). However, a novel miR-146A upstream variant (C/A at 5:160,485,254) was discovered in one case with autism. Methylation and common genetic variations in miR-146A and miR-146B are unlikely to play significant roles in ASD in this population. The discovery of a novel upstream variant highlights the potential importance of regulatory regions in miRNA function. Further studies with larger cohorts and functional validation are recommended.

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6. Singh K, Shukla S, Kumari AP, Qurashi A, Verma AK, Kumar A. Repurposing Nitazoxanide to target the expanded r(CGG)(n) repeat RNA for therapeutic intervention in fragile-X tremor/ataxia syndrome. Int J Biol Macromol. 2025; 329(Pt 2): 147864.

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a debilitating neurodegenerative disorder linked to CGG trinucleotide repeat expansions in the FMR1 gene. These expanded repeats produce toxic FMR1poly-Glycine (FMR1polyG) proteins in neurons through mechanisms such as Repeat-Associated Non-AUG (RAN) translation and RNA foci formation, driving disease progression. In this study, we investigate the potential of Nitazoxanide (NTZ), a broad-spectrum antiparasitic and antiviral medication, as a therapeutic agent for FXTAS by targeting CGG repeat-associated toxicity. This comprehensive approach utilizing biophysical techniques, bioinformatic studies, cellular assays, and Drosophila models reveals NTZ’s remarkable ability to bind specifically to toxic CGG repeat RNA, particularly GG mismatches, and to inhibit FMR1polyG aggregation. Biophysical methods, including Circular Dichroism (CD), Isothermal Titration Calorimetry (ITC), Electrophoretic Mobility Shift assays (EMSA), and Nuclear Magnetic Resonance (NMR) spectroscopy, accompanied with Molecular Docking, confirmed that NTZ effectively binds to CGG repeat RNA and mitigates its toxicity. Moreover, treatment with NTZ significantly reduced FMR1polyG-associated toxicity, corrected the splicing defects in FXTAS cell models, and improved different phenotypes in the Drosophila model of FXTAS. These compelling findings position NTZ as a promising candidate for neuroprotection in FXTAS, indicating its remarkable therapeutic potential and paving the way for future clinical applications to improve outcomes for the affected patients.

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7. Sun C, McEwan A, Boulton KA, Demetriou EA, Sadozai AK, Lampit A, Guastella AJ. Artificial intelligence for tracking social behaviours and supporting an autism spectrum disorder diagnosis: systematic review and meta-analysis. EBioMedicine. 2025; 120: 105931.

BACKGROUND: Artificial intelligence (AI) holds promise for developing tools that can track social behaviours and support clinical assessments and outcomes in Autism Spectrum Disorders (ASD). This review evaluated existing AI algorithms for extracting facial information during social interaction assessments and contributing to diagnostic accuracy for ASD assessment and response to therapy. METHODS: Systematic review of studies on human participants with an ASD diagnosis, sourced from Medline, Embase, Scopus, Web of Science, IEEE Xplore, and ACM Digital Library, evaluated the diagnostic accuracy of AI algorithms in ASD classification and their use in tracking social development through facial information for clinical application in social interactions. Bivariate and multi-level models addressed dependencies, heterogeneity, moderators (modalities, algorithms, tasks), and applied robust variance estimation. Publication bias was evaluated with funnel plots. The QUADAS-2 tool assessed the risk of bias and applicability. This study was registered on PROSPERO (CRD42021249905). FINDINGS: Of 40,570 studies identified, 38 met the review criteria, and seven provided sufficient data for meta-analysis. The pooled diagnostic odds ratio of 15.917 (95% CI [4.775-53.059]), and bivariate analysis estimated an area under the receiver operating characteristic curve of 0.862. Accuracy improved with facial features, unstructured play, support vector machines, and decision tree-based algorithms. AI methods can analyse social behaviours, including eye gaze on social stimuli, emotional expression, and joint attention in ASD assessments. AI-enabled robots have also been used to guide therapy. INTERPRETATION: This study shows that AI can accurately and objectively augment ASD assessments, track social behaviours, and enhance therapy outcomes. Further validation in diverse populations is needed to ensure clinical applicability and ethical use. FUNDING: None.

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8. Torres-Gonzalez L, Morgan SJ, Truong WH, Palmer C, Nouraee C, Harding DC. Scoliosis in adolescents with autism spectrum disorder: A retrospective case series. J Child Orthop. 2025: 18632521251379277.

PURPOSE: To describe the curve patterns and behaviors, clinical presentation, treatment modalities, and complications for adolescents with both scoliosis and autism spectrum disorders, but no additional concomitant diagnoses. METHODS: A single-center, retrospective review of adolescents with scoliosis and autism spectrum disorder treated between 2001 and 2021. Patient demographics, clinical characteristics, and radiographic assessments were described across the scoliosis treatment plans (i.e. observation, bracing, and surgery). RESULTS: Forty patients with scoliosis and autism spectrum disorder (80% male, mean age at 13.2 ± 1.7) met eligibility criteria. Twenty-one patients were managed with observation initially. Of these patients, 55% (n = 11) didn’t require further treatment and had an average change in curvature of 5° ± 6°. Twenty-one total patients were managed with bracing. In this group, 76% (n = 16) did not receive further treatments and had an average increase in curvature of 15° ± 11°. Five patients (24%) proceeded to surgery following brace treatment. Thirteen patients (33%) in total required surgery, with n = 5 requiring surgery as their initial treatment. The initial curve magnitude for this group was 55° ± 7° and had an average correction of 47% following posterior spinal fusion. CONCLUSIONS: Although curves in adolescents with scoliosis and autism spectrum disorder had a similar presentation to adolescents with just scoliosis, the current cohort did have an increase in curve progression when managed with bracing, with an unclear explanation. Further study is warranted in this unique population, and families should be counseled that the prognosis may not be the same as adolescents with scoliosis alone. LEVELS OF EVIDENCE: Level IV.

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