Journal of Neurodevelopmental Disorders最新文献

{"title":"Memory, attention, and executive function in intellectual and developmental disabilities.","authors":"Tanya St John, Gabriel S Dichter, Sigan Hartley","doi":"10.1186/s11689-026-09734-9","DOIUrl":"10.1186/s11689-026-09734-9","url":null,"abstract":"","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using eye tracking to explore the relationship between autism traits, joint attention, cognition and adaptive functioning in preschool children.","authors":"Anthea A Stylianakis, Hannah Pincham, Sparsh Chawla, Nisha E Mathew, Valsamma Eapen","doi":"10.1186/s11689-026-09714-z","DOIUrl":"10.1186/s11689-026-09714-z","url":null,"abstract":"<p><p>There is significant heterogeneity in clinical presentations, brain-imaging findings, and genetic underpinnings of autism. Autism traits, particularly social affect and joint attention, and related domains of adaptive functioning and cognitive development, are key characteristics in determining autism \"profiles\". This study aimed to understand such baseline profiles in preschool autistic children receiving early intervention (age range, 2-7 years old; sample size N = 67). We also examined the association between phenotypic pre-intervention characteristics and response to intervention using Early Start Denver Model (ESDM). Baseline characteristics prior to receiving early intervention demonstrated a link between eye tracking measure of joint attention, namely better gaze accuracy, and clinical profile of autism traits, particularly better social affect/social overtures and adaptive functioning. Further, better receptive and expressive language, visual reception and fine motor skills, and higher development quotients on a visual processing task, were found to be associated with more accurate eye movements on a joint attention task. Predictors of improvement in autistic traits post-intervention included higher age at entry to intervention and baseline developmental functioning. Specifically, social affect was found to change in the same direction as cognitive functioning post-ESDM intervention, especially with regard to visual reception, fine motor and receptive language skills. The findings also suggest that better social affect and joint attention, characterised by better social overtures and maintenance of attention, are predictive of more accurate eye gaze in a social exercise, thereby making these potential intervention targets in early intervention.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotyping iPSC-derived neurons from Angelman patients and partial rescue via JNK pathway inactivation.","authors":"Valentina Alari, Clara Cambria, Chiara De Cesari, Alessandro Vimercati, Milena Crippa, Sara Perego, Lidia Larizza, Ilaria Tonazzini, Flavia Antonucci, Silvia Russo","doi":"10.1186/s11689-026-09728-7","DOIUrl":"10.1186/s11689-026-09728-7","url":null,"abstract":"<p><strong>Background: </strong>Angelman Syndrome (AS, MIM #105,830) is a rare neurodevelopmental disorder caused by imprinting defects, and it is marked by motor impairment, intellectual disability, speech limitations, and seizures. The condition arises due to the loss of function in neurons of the maternally-inherited UBE3A gene, mapping in the imprinted chromosomal region 15q11.2-q13, through a variety of genetic and epigenetic mechanisms. UBE3A encodes a ubiquitin E3 ligase, which is essential for synaptic plasticity. Most studies of AS have been performed on animal models, while induced pluripotent stem cells (IPSCs), mainly generated from patients with deletion, remain limited in number.</p><p><strong>Methods: </strong>Here we report on the generation and characterization of human cortical neurons derived from IPSCs obtained from children representative of the main AS genotypes: 3 with 15q11-13 deletion, 3 with UBE3A mutations, 3 with uniparental disomy, and 2 with imprinting defects.</p><p><strong>Results: </strong>During early neuronal differentiation, morphological analyses highlighted a reduced dendritic branching and an increased number of thin filopodia, while migration assays revealed reduced neurite mobility in AS human neurons with the most severe genetic defect, namely the 15q11-13 deletion. At a later differentiation time point, electrophysiological analyses revealed impaired neuronal activity in AS patient-derived neurons. To investigate pathways potentially involved in synaptic dysfunction, we examined the JNK (c-Jun N-terminal kinase) signalling pathway, which plays key roles in neuroinflammation and synaptic development. We found increased JNK activation and, importantly, treatment with a JNK-inhibitor, D-JNKI1, partially rescued the neuronal morphological defects, significantly reducing the number of immature protrusions, as well as defects in electrophysiological properties.</p><p><strong>Conclusions: </strong>Our patient-specific models contribute elucidate how loss of UBE3A leads to aberrant neuronal maturation and function in the precocious stages of neuronal development and how treatment with D-JNKI1 may pave the way for new therapeutic possibilities.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascading effect of early sensory differences on subsequent autistic traits in infants later diagnosed with autism: a prospective cohort study.","authors":"Shihuan Wang, Cong You, Kaiyun Chen, Linru Liu, Yu Xing, Shaoli Lv, Yuanyuan Zou, Fengjing Liang, Yanting Xu, Qianying Ye, Yijie Li, Leran Xue, Feixia Zhang, Hongzhu Deng","doi":"10.1186/s11689-026-09725-w","DOIUrl":"10.1186/s11689-026-09725-w","url":null,"abstract":"<p><strong>Background: </strong>Sensory differences constitute core diagnostic features of autism. The cascading effect model posits that early sensory differences may be prospectively associated with subsequent autistic traits, whereas empirical evidence in infancy remains scarce. This study aims to characterize trajectory differences of early sensory profiles and examine the cascading effect on subsequent autistic traits in infants later diagnosed with autism.</p><p><strong>Methods: </strong>In this prospective longitudinal study, 134 Chinese infants were followed from 12 to 36 months of age. Trajectory differences in four sensory profiles (sensitivity, avoiding, registration, and seeking) were compared between diagnostic groups using the Toddler Sensory Profile-2. The cascading effect were examined through Structural Equation Modeling and temporally ordered path analysis to test direct and indirect effects of early sensory differences on subsequent autistic traits via the mediation of social skills in autism.</p><p><strong>Results: </strong>Compared to typical development, infants later diagnosed with autism exhibited significantly elevated sensory sensitivity and sensory avoiding, along with elevated sensory registration scores at 12 months, with sensory sensitivity showing differential trajectories over time (F = 3.25, p = 0.004). Elevated sensory avoiding at 18 months exerted an indirect effect on social-communication at 36 months via the mediating role of social skills at 24 months (B = 0.08, p = 0.007). Additionally, temporally ordered path analysis revealed that elevated sensory avoiding at 18 months negatively predicted social skills at 24 months (β = -0.19, p = 0.030). Notably, in an exploratory analysis, increased sensory seeking at 18 months positively predicted adaptive skills at 36 months (B = 0.97, p = 0.031).</p><p><strong>Conclusions: </strong>Sensory differences emerge as early as 12 months in infants who later receive an autistic diagnosis, with sensory sensitivity demonstrating distinct developmental trajectories. These findings provide prospective evidence to support the cascading effect model in autism, identifying early sensory avoiding as an important early correlate of subsequent social-communicative development. Furthermore, early sensory seeking behaviors may facilitate subsequent adaptive functioning, highlighting the heterogeneous developmental pathways within autism.</p><p><strong>Trial registration: </strong>www.chictr.org.cn ; Trial No: ChiCTR2100049811; Trial Date:2021.08.10.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Working memory and language development have a bi-directional longitudinal relationship in autistic preschoolers.","authors":"Aanya Sehgal, Gina Schnur, Viviane Valdes, Susan Faja","doi":"10.1186/s11689-026-09712-1","DOIUrl":"https://doi.org/10.1186/s11689-026-09712-1","url":null,"abstract":"<p><strong>Background: </strong>Among neurotypical children working memory and language development are closely related, but the longitudinal relationship between these factors is unknown in autism. This study had the goal of evaluating potential bidirectional relationships between these domains.</p><p><strong>Methods: </strong>A longitudinal design included language and visuospatial working memory assessments across three time points with 160 autistic preschoolers. Time points were one year apart. A cross-lagged panel model (CLPM) using Full-Information Maximum Likelihood (FIML) was used to evaluate longitudinal associations between performance on a working memory task (i.e., the Hide and Seek Task) and language scores (i.e., verbal development quotient).</p><p><strong>Results: </strong>Cross-lagged associations were significant for paths from working memory at the first time point to language at the second time point (β = .31, p = .01) and from language at first time point to working memory at the second time point (β = .40, p < .001). Cross-lagged paths from the second to third time point were not statistically significant in either direction.</p><p><strong>Conclusions: </strong>This study provides evidence of a bidirectional relationship between working memory and language in autistic toddlers and preschoolers among younger autistic preschoolers. These results highlight working memory as a potential early assessment and intervention domain for improving language outcomes in autism as well as the role of language delays as a factor related to reduced working memory skills later in development.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of EEG neurofeedback in adults with attention-deficit/hyperactivity disorder: a systematic review of randomised and non-randomised studies.","authors":"Małgorzata Rotkiewicz, Yassine Yachou, Sofia Charef, Noomane Bouaziz, Dominique Januel","doi":"10.1186/s11689-026-09720-1","DOIUrl":"https://doi.org/10.1186/s11689-026-09720-1","url":null,"abstract":"<p><strong>Background: </strong>Pharmacotherapy is recommended as the first-line treatment for adult attention-deficit/hyperactivity disorder (ADHD), yet some individuals show partial or inadequate response associated with adverse effects. These limitations have prompted interest in adjunctive or alternative interventions. Electroencephalography (EEG) neurofeedback is a non-pharmacological intervention for ADHD, which enables self-regulation of neural activity. This systematic review synthesised clinical, cognitive, and electrophysiological outcomes of EEG neurofeedback in adult ADHD, and examined standard versus personalised training protocols.</p><p><strong>Methods: </strong>Following PRISMA guidelines, four databases (PubMed, ScienceDirect, Ovid, Web of Science) were searched from 1960 to October 2025 for this PROSPERO-registered review (ID: CRD420251020898). Eligible studies included adults (≥ 18 years) with a formal ADHD diagnosis undergoing EEG neurofeedback. Outcomes comprised symptom severity, cognitive performance, electrophysiology, and adverse events. Risk of bias was assessed using RoB 2 and ROBINS-I V2.</p><p><strong>Results: </strong>Seven studies (three RCTs, four non-randomised; n = 390) met inclusion criteria. Protocols included theta/beta (n = 1), slow cortical potential (n = 1), alpha downregulation training (n = 1) and personalised approaches guided by individual alpha peak frequency (n = 3) or QEEG profiles (n = 1). Naturalistic and personalised studies reported large symptom reductions, whereas RCTs revealed small, generally non-significant effects relative to controls. Cognitive improvements were inconsistently reported and largely attributable to practice effects. Electrophysiological changes were protocol-specific without convergence across studies. No treatment-related adverse events were observed.</p><p><strong>Conclusions: </strong>Evidence remains limited by methodological heterogeneity, small samples, variable controls, inconsistent learning metrics, and risk of bias. Current RCTs do not demonstrate evidence of efficacy over placebo. Blinded, adequately powered trials using standardised learning measures are needed to clarify mechanisms of neurofeedback.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caregiver-reported relevance of the BRIEF-2 in youth with Down syndrome: an initial content validity study.","authors":"Natasha N Ludwig, Mary Godfrey, Rebekah Bosley, Alexandria Barkhimer, Luther G Kalb, Vini Singh, Amy Cohen, Tracie C Rosser, Laura J Mattie, George T Capone, Marie Moore Channell, Lisa A Jacobson","doi":"10.1186/s11689-026-09715-y","DOIUrl":"https://doi.org/10.1186/s11689-026-09715-y","url":null,"abstract":"<p><strong>Background: </strong>Establishing evidence of content validity, or how well a measure reflects the intended outcome, is essential for developing or selecting assessment tools that support individualized care and research in clinical populations like Down syndrome (DS). This study aimed to examine caregiver-reported relevance of a widely used measure of executive function in school-aged youth with DS, the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Parent Form. Specifically, this study focused on one aspect of content validity, relevance to the target population, which has yet to be systematically evaluated in DS.</p><p><strong>Methods: </strong>This study integrated data from two online studies of youth with DS. After completing the BRIEF-2, caregivers were asked forced-choice questions about the relevance of the measure to their child with DS, as well as an open-text question about their response strategy for items they deemed not relevant.</p><p><strong>Results: </strong>Caregivers of 281 youth with DS between the ages of 6-18 years (M = 12.7, SD = 3.4) reported on the relevance of the BRIEF-2 for their child. Just under half (46.3%) of caregivers reported that they deemed items not relevant. Of those caregivers who deemed items not relevant, just over half (57.7%) described their response strategy was to select \"Never\" for items that were not relevant; however, a range of strategies was employed. Caregivers rated the measure overall as moderately relevant to their child, although there was considerable range in ratings. Additionally, caregivers of youth who were ≤ 12 years old, had lower expressive language skills (i.e., no phrases/sentences) or lower adaptive function (> 2 SDs below the mean), rated items as not relevant to their child more often and provided lower overall measure relevance ratings than caregivers of youth who were older and/or had stronger functional skills.</p><p><strong>Conclusions: </strong>This initial evaluation of the content validity of the BRIEF-2 in school-aged youth with DS indicates that there is a range of caregiver viewpoints about measure relevance. Findings highlight the need for more comprehensive studies that engage patients/families and professionals to better understand the broader content validity of the BRIEF-2 in DS across ages and developmental levels to inform any modifications for use in future clinical and research contexts.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding clinical variability in FBXW7-related neurodevelopmental disorder: a multicenter case series.","authors":"Salvatore Savasta, Francesco Fabrizio Comisi, Giovanni Battista Dell'Isola, Gabriele Di Pasquale, Ivy Johnson, Isabella Herman, Andrea Maria Comisi, Francesca Felicia Operto, Giuditta Bargiacchi, Daniëla Q C M Barge-Schaapveld, Giuseppe Donato Mangano, Marco Carotenuto, Vincenzo Salpietro, Alberto Verrotti","doi":"10.1186/s11689-026-09705-0","DOIUrl":"10.1186/s11689-026-09705-0","url":null,"abstract":"<p><strong>Background: </strong>Heterozygous variants in FBXW7 have recently been recognized as a cause of a rare neurodevelopmental disorder with variable developmental delay, neurological manifestations, and multisystem involvement. The breadth of clinical variability and penetrance remains incompletely defined.</p><p><strong>Cases presentation: </strong>We report a retrospective multicenter case series of seven previously unreported individuals (five males, two females) with heterozygous FBXW7 variants identified through clinical genetic testing, aged 5-9 years at last evaluation (median 6 years). Six variants occurred de novo and one was inherited. Neurodevelopmental involvement was present in six individuals and was characterized by global developmental delay and language impairment; hypotonia was observed in all seven. Formal intellectual disability was documented in four cases, while one individual showed preserved cognitive functioning with predominant behavioral difficulties. Epileptic seizures occurred in four individuals, whereas three had no history of epilepsy. Brain MRI was available for six individuals and was normal in four, whereas two showed structural anomalies involving the corpus callosum. Extracerebral features were variably reported, most commonly constipation and recurrent respiratory/otolaryngological infections. Comparison with previously reported individuals confirmed the core neurodevelopmental phenotype and further refined the spectrum.</p><p><strong>Conclusions: </strong>This case series expands the phenotypic spectrum associated with FBXW7-related neurodevelopmental disorder and highlights variable expressivity and incomplete penetrance, including clinically relevant variants presenting with mild or atypical phenotypes. These findings support considering FBXW7 across a broad range of neurodevelopmental presentations and inform genetic counseling.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Processing of emotional faces has unique functional and cytoarchitectural associations in those with an autism spectrum diagnosis.","authors":"Zachary P Christensen, Edward G Freedman, John J Foxe","doi":"10.1186/s11689-026-09716-x","DOIUrl":"10.1186/s11689-026-09716-x","url":null,"abstract":"<p><p>Those with an autism spectrum diagnosis (ASD) have been found to process emotional faces differently than other populations. Processing of emotional faces requires engagement of temporal, frontal, occipital, and limbic brain regions. Functional activity has been shown to differ in those with an ASD, particularly in the amygdala, inferior frontal cortex (IFC), and temporal brain regions. However, the consistency and direction of these associations have been inconsistent across studies. Recent findings have demonstrated that measures of neuron density differ in those with an ASD. Some of these regional differences in cytoarchitecture coincide with regions important to emotional facial processing. Therefore, the interaction between cytoarchitecture and functional activity may be important in elucidating unique neurophysiology in ASD. The present study uses diffusion weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data from the Adolescent Brain Cognitive Development^sm (ABCD®) study to investigate the relationship between cytoarchitecture and functional activity during emotional face processing in those with an ASD. 149 individuals with a reported ASD and 10,146 individuals with no reported diagnosis of an ASD (nASD) were identified. The emotional n-back (EN-Back) task was administered during fMRI acquisition, activating regions of the brain associated with processing emotional faces. Neuron cell body density was positively correlated with functional activation in the left amygdala in the ASD group but not the nASD group. These findings suggest that a unique relationship may exist between neuron cell body density in the left amygdala and functional activity while processing emotional faces in those with an ASD.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-chromosomal genetic variants and haplotype analysis in male cerebral palsy patients: insights into genetic susceptibility and sex-specific risk.","authors":"Yu Su, Yangong Wang, Ye Cheng, Yiran Xu, Yimeng Qiao, Lei Xia, Juan Song, Yunqian Li, Junjie Zhang, Hongyuan Sun, Xiaoyang Wang, Changlian Zhu, Qinghe Xing","doi":"10.1186/s11689-026-09717-w","DOIUrl":"10.1186/s11689-026-09717-w","url":null,"abstract":"<p><strong>Background: </strong>Cerebral palsy (CP) is a neurodevelopmental disorder with a significant male predisposition, yet the underlying genetic mechanisms driving this sex-specific risk remain poorly understood. Given the hemizygous state of X-linked variants in males, we hypothesized that X-chromosomal genetic variations may contribute to CP susceptibility in male patients.</p><p><strong>Methods: </strong>We performed an X-chromosome-wide association study (XWAS) using whole-exome sequencing (WES) data from 1,076 male CP patients and 1,057 healthy male controls of Chinese ancestry. Quality control, principal component analysis (PCA), and logistic regression were applied to identify risk loci for CP. Six candidate single nucleotide variants (SNVs) in UTP14A were genotyped via MassARRAY, and haplotype analysis was conducted using SHEsis.</p><p><strong>Result: </strong>We identified a significant association between the intronic variant rs2281277 in UTP14A and CP (P = 1.38E-05, FDR q-value = 0.0465, OR = 0.644). In addition to the lead SNV rs2281277, five other SNVs in UTP14A also showed a suggestive association with CP, including rs141750783, rs61318448, rs2273021, rs2281278, and rs111975985. Haplotype analysis further revealed a risk haplotype (CGTATC) defined by these six SNVs, which was associated with a 53.1% increased susceptibility to CP (P = 9.40E-8, OR = 1.531).</p><p><strong>Conclusion: </strong>This study nominates X-linked UTP14A as a candidate susceptibility locus for CP in male Chinese, which warrants replication based on large, independent cohorts and functional validation.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}