Background: In Italy, there is a lack of reliable data on the epidemiology of Autism Spectrum Disorder (ASD) on a national scale. The exact etiopathogenesis of ASDs is still largely unknown, with autism representing t...Background: In Italy, there is a lack of reliable data on the epidemiology of Autism Spectrum Disorder (ASD) on a national scale. The exact etiopathogenesis of ASDs is still largely unknown, with autism representing the final common pathway of different pathological conditions. Aim of the Study: Assessment of the effects produced by the individualised, intensive and holistic rehabilitation programme used by the Il Cireneo Foundation on the daily living skills of people diagnosed with ASD. Materials and Methods: Out of the eighty-seven (n = 87) enrolees, seventy-nine (n = 79), of whom 19 were females (24.1%) and 60 were males (75.9%), with a mean age of 13.41 years (SD = 6.93 years;range = 2 - 33 years) terminated the three-year study. The enrolees were evaluated two times: at the beginning of the rehabilitation programme and at the end of the three-year goal-oriented project. Results: Statistically significant results between T0 and T1 were recorded for CARS (t-4.221;p Conclusions: People diagnosed with autism can be helped to become more autonomous and independent in carrying out activities of daily living thanks to an intensive psycho-educational and cognitive-behavioural rehabilitation programme, of which the Il Cireneo Foundation is the only expression in the Abruzzo region.展开更多
BACKGROUND Managing critical care emergencies in children with autism spectrum disorder(ASD)presents unique challenges due to their distinct sensory sensitivities,communication difficulties,and behavioral issues.Effec...BACKGROUND Managing critical care emergencies in children with autism spectrum disorder(ASD)presents unique challenges due to their distinct sensory sensitivities,communication difficulties,and behavioral issues.Effective strategies and protocols are essential for optimal care in these high-stress situations.AIM To systematically evaluate and synthesize current evidence on best practices for managing critical care emergencies in children with ASD.The review focuses on key areas,including sensory-friendly environments,communication strategies,behavioral management,and the role of multidisciplinary approaches.METHODS A comprehensive search was conducted across major medical databases,including PubMed,Embase,and Cochrane Library,for studies published between 2000 and 2023.Studies were selected based on their relevance to critical care management in children with ASD,encompassing randomized controlled trials,observational studies,qualitative research,and case studies.Data were extracted and analyzed to identify common themes,successful strategies,and areas for improvement.RESULTS The review identified 50 studies that met the inclusion criteria.Findings highlighted the importance of creating sensory-friendly environments,utilizing effective communication strategies,and implementing individualized behavioral management plans.These findings,derived from a comprehensive review of current evidence,provide valuable insights into the best practices for managing critical care emergencies in children with ASD.Sensory modifications,such as reduced lighting and noise,visual aids,and augmentative and alternative communication tools,enhanced patient comfort and cooperation.The involvement of multidisciplinary teams was crucial in delivering holistic care.Case studies provided practical insights and underscored the need for continuous refi-nement of protocols.CONCLUSION The review emphasizes the need for a tailored approach to managing critical care emergencies for children with ASD.Sensory-friendly adjustments,effective communication,and behavioral strategies supported by a mul-tidisciplinary team are integral to improving outcomes.Despite progress,ongoing refinement of care practices and protocols is necessary.This ongoing process addresses remaining challenges and engages healthcare professionals in continuous improvement of care for children with ASD in critical settings.展开更多
We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies wer...We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.展开更多
Objective Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by difficulties with communication and social interaction,restricted and repetitive behaviors.Previous studies have indicated that...Objective Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by difficulties with communication and social interaction,restricted and repetitive behaviors.Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits,which are closely related to the core symptoms of ASD.Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities.Therefore,this study explores the behavior of children with ASD in capturing attention to changes in topological properties.Methods Our study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing(TD)age-matched controls.In an attention capture task,we recorded the saccadic behaviors of children with ASD and TD in response to topological change(TC)and non-topological change(nTC)stimuli.Saccadic reaction time(SRT),visual search time(VS),and first fixation dwell time(FFDT)were used as indicators of attentional bias.Pearson correlation tests between the clinical assessment scales and attentional bias were conducted.Results This study found that TD children had significantly faster SRT(P<0.05)and VS(P<0.05)for the TC stimuli compared to the nTC stimuli,while the children with ASD did not exhibit significant differences in either measure(P>0.05).Additionally,ASD children demonstrated significantly less attention towards the TC targets(measured by FFDT),in comparison to TD children(P<0.05).Furthermore,ASD children exhibited a significant negative linear correlation between their attentional bias(measured by VS)and their scores on the compulsive subscale(P<0.05).Conclusion The results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection.This atypical attention may affect the child’s cognitive and behavioral development,thereby impacting their social communication and interaction.In sum,our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.Th...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.展开更多
Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and ...Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.展开更多
This article describes a pilot study aiming at generating social interactions between a humanoid robot and adolescents with autism spectrum disorder (ASD), through the practice of a gesture imitation game. The partici...This article describes a pilot study aiming at generating social interactions between a humanoid robot and adolescents with autism spectrum disorder (ASD), through the practice of a gesture imitation game. The participants were a 17-year-old young lady with ASD and intellectual deficit, and a control participant: a preadolescent with ASD but no intellectual deficit (Asperger syndrome). The game is comprised of four phases: greetings, pairing, imitation, and closing. Field educators were involved, playing specific roles: visual or physical inciter. The use of a robot allows for catching the participants’ attention, playing the imitation game for a longer period of time than with a human partner, and preventing the game partner’s negative facial expressions resulting from tiredness, impatience, or boredom. The participants’ behavior was observed in terms of initial approach towards the robot, positioning relative to the robot in terms of distance and orientation, reactions to the robot’s voice or moves, signs of happiness, and imitation attempts. Results suggest a more and more natural approach towards the robot during the sessions, as well as a higher level of social interaction, based on the variations of the parameters listed above. We use these preliminary results to draw the next steps of our research work as well as identify further perspectives, with this aim in mind: improving social interactions with adolescents with ASD and intellectual deficit, allowing for better integration of these people into our societies.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental disorder that manifests in the first years of life,with a complex pathogenesis influenced by biological,genetic and epigenetic factors.Many children with...BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental disorder that manifests in the first years of life,with a complex pathogenesis influenced by biological,genetic and epigenetic factors.Many children with ASD display marked food selectivity,often restricting themselves to a narrow range of foods.The problems associated with feeding children with ASD can vary widely,from mild cases that pose no immediate health risks,to more severe situations with a risk of mal-nutrition or,conversely,overeating.This scoping review aims to provide an in-depth overview of the frequency,nature and factors related to food selectivity in children with autism.AIM To comprehensively review the literature on food selectivity in ASD.METHODS A systematic review of the literature was conducted using the PubMed,Web of Science and EBSCO databases,to identify articles published in English from 2014 until 2024.Studies on a sample diagnosed with ASD and food selectivity were included.The selected databases were chosen for their broad coverage of the scientific literature.These databases represent reliable sources of high-quality articles,ensuring a comprehensive and up-to-date search.RESULTS We evaluated 222 studies on food selectivity in autism,from which duplicates were removed and unrelated titles were filtered out.Finally,9 articles were included in the review.Five articles provide a general overview of the phenomenon,analysing its nature and factors.Two studies delve into sensory sensitivity,in particular the impact of food textures,tastes and smells.Finally,two studies focus on problem behaviour during mealtimes.CONCLUSION Children with ASD have greater food selectivity than the neurotypical population.The diet should contain a greater variety of fruit,vegetables,yoghurt,while reducing the consumption of rice and pasta.展开更多
To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial mag...To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial magnetic stimulation(rTMS),one of the most commonly applied non-invasive neurostimulation techniques,has shown efficacy in treating neuropsychiatric disorders,such as depression.展开更多
Autism spectrum disorder(ASD)is an early-onset neurodevelopmental disorder marked by persistent deficits in social communication and interaction,alongside restricted,repetitive patterns of behaviors(RRB),interests,or ...Autism spectrum disorder(ASD)is an early-onset neurodevelopmental disorder marked by persistent deficits in social communication and interaction,alongside restricted,repetitive patterns of behaviors(RRB),interests,or activities.It often co-occurs with various neuropsychiatric disorders,though their frequency varies widely due to unclear boundaries between the core features of ASD and common comorbidities.Catatonia,increasingly noted in neurodevelopmental conditions like ASD,shares striking similarities with ASD in symptomatology,brain mech-anisms,and treatment responses,prompting the question of whether it is a core feature of ASD or a distinct condition.This paper delved into this overlap,ex-ploring the relationship between catatonia and ASD through a narrative review of peer-reviewed literature from 1943 to 2024,sourced from PubMed and psy-chiatric journals.Focusing on ASD diagnostic evolution,symptom overlap with catatonia,and shared neurobiological and therapeutic characteristics,we used thematic analysis to synthesize findings into key areas such as historical nosology,phenomenological overlap,neurobiological parallels,and treatment response.The evidence revealed weak support for separating catatonia from overlapping RRB features of ASD,suggesting that some RRB might align more with comorbid catatonia than intrinsic ASD traits.However,this idea needs further validation through rigorous clinical trials.Clarifying this relationship could refine diagnostic approaches and open doors to targeted treatments,potentially improving out-comes for those affected.展开更多
The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide.Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via...The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide.Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via heavy metal exposures and nutritional deficits that impact the expression of genes.In the case of the metallothionein(MT)gene,biomarker studies show dietary zinc(Zn)deficits impact MT protein levels in children with autism and are associated with the bioaccumulation of lead and/or mercury in children exhibiting autism/attention deficit/hyperactivity disorders symptomology.The impact of dietary changes on lead and mercury exposures and MT gene behavior could be determined using a randomized test and control group design.Pregnant women serving in the testgroup would participate in a nutritional epigenetics education intervention/course designed to reduce ultra-processed food intake and heavy metal levels in blood while increasing whole food intake and MT and Zn levels.Changes in maternal diet would be measured using data derived from an online diet survey administered to the test and control groups pre-post intervention.Changes in maternal lead,mercury,Zn,and MT levels would be measured via blood sample analyses prior to the intervention and after childbirth via cord blood analyses to determine infant risk factors.展开更多
BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as ...BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.展开更多
Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psych...Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psychiatric,and behavioral issues,highlighting the urgent need for autism-competent healthcare providers in general healthcare.This review aims to equip primary care providers(PCPs)with a concise summary of common CCs and strategies for effective identification.A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature,research evidence,and existing clinical trial outcomes,supplementing their clinical expertise.Autistic children consistently show higher rates of both medical and mental health issues.Despite greater healthcare utilization,many autistic individuals report unmet needs.CCs can impair behavior,functioning,and well-being,but are often treatable when recognized early.Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families.This evidence-based review supports PCPs in enhancing their knowledge,fostering early recognition,and delivering comprehensive,responsive care.展开更多
Background:Parents of children with autism are susceptible to parenting burnout due to tremendous parenting burden and parenting challenges.Parenting burnout has a detrimental effect on both children with autism and t...Background:Parents of children with autism are susceptible to parenting burnout due to tremendous parenting burden and parenting challenges.Parenting burnout has a detrimental effect on both children with autism and their parents.However,the underlying mechanisms that lead to parenting burnout remain unclear.This study aimed to investigate the relationship between parenting stress and parenting burnout,along with the serial mediation effect of social support and coping strategies in the context of families with autistic children.Methods:We conducted a cross-sectional study in 231 parents of autistic children in four autism facilities located in central Hubei province.Data were collected through the Parental Stress Index,Social Support Rating Scale,Simplified Coping Strategies Questionnaire,and Caregiver Burnout Assessment Questionnaire.Results:Parenting stress and burnout status were:72.3%of parents reported high-stress levels,16.9%experienced risks for parenting burnout,and 19.9%were currently experiencing burnout.Both social support and coping strategies played partial mediating roles in the relationship between parental stress and burnout,forming a serial mediation effect.Conclusion:Parenting stress is a risk factor for parenting burnout.Social support and coping strategies play a chain mediating role between parenting stress and parenting burnout,which may act as the underlying mechanisms.The study offers insights into potential intervention points for reducing parenting burnout.Future efforts are needed to devote to parenting stress,social support and coping strategy to enhance the psychological well-being of parents with autistic children.展开更多
Autism spectrum disorder(ASD)poses significant challenges for families,with limited access to specialized care being a critical concern.The coronavirus disease 2019 pandemic has accelerated the adoption of remote supp...Autism spectrum disorder(ASD)poses significant challenges for families,with limited access to specialized care being a critical concern.The coronavirus disease 2019 pandemic has accelerated the adoption of remote support,highlighting its potential to enhance family-centered care for children with ASD.In this editorial,we comment on the article by Lu et al,emphasizing the effectiveness of integrating remote support courses with traditional caregiver-mediated interventions.We further explore the benefits of remote support in delivering family-centered care,summarize the essential components of effective family-centered remote support,outline key considerations for implementation,and discuss potential future research directions.We conclude that family-centered remote support has the potential to significantly improve outcomes and quality of life for individuals with ASD and their families.展开更多
Autism spectrum disorder(ASD)represents a neurodevelopmental disorder that has been the focus of numerous studies on the central nervous system(CNS).The embryological origin of the brain and retina is shared,with the ...Autism spectrum disorder(ASD)represents a neurodevelopmental disorder that has been the focus of numerous studies on the central nervous system(CNS).The embryological origin of the brain and retina is shared,with the axons of retinal ganglion cells(RGC)developing into the optic nerves that enter the brain through the dorsal lateral geniculate nucleus(LGN)of the thalamus,LGN,and other visual cortices.Given the evidence that individuals with ASD exhibit impairments in the visual mechanisms,including deficits in emotional face recognition,and difficulty in maintaining gaze control as well as eye contact,some studies have documented retinal alterations in individuals with ASD.These have been identified through ophthalmic assessments,including optical coherence tomography(OCT),optical coherence tomography angiography(OCTA),and electroretinography(ERG).With the improvements in ASD animal models,it is possible to obtain a better understanding of vision dysfunction in ASD by analyzing the molecular mechanisms of retinal function and structure abnormalities.This review aims to provide a summary of the recent research on ocular alterations in ASD patients and animal models,intending to contribute to further investigation of the eye-brain connection and communication.展开更多
One of the core challenges faced by children with autism is repetitive motor behavior,which not only undermines their learning efficiency in the classroom but also makes it difficult for them to integrate smoothly int...One of the core challenges faced by children with autism is repetitive motor behavior,which not only undermines their learning efficiency in the classroom but also makes it difficult for them to integrate smoothly into inclusive educational settings,thereby hindering their social adaptation and overall development.This study adopted a single-case design focusing on a first-grade student with autism enrolled in a mainstream class at Xiangxue Primary School,Huangpu District,Guangzhou.Functional behavior assessment was conducted to systematically observe and analyze the student’s repetitive motor behaviors in class,on the basis of which an intervention plan was developed and implemented.The intervention incorporated antecedent control,replacement behavior training,and consequence management,supplemented by collaboration between school and family.The findings indicated that the frequency of repetitive motor behaviors decreased significantly after the intervention,while the student demonstrated improved classroom participation and peer interaction;these positive effects were maintained during the follow-up phase.The study suggests that in inclusive education settings,interventions guided by functional behavior assessment can effectively reduce problem behaviors in children with autism and enhance their classroom engagement and learning adaptability.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule ...Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule membrane(GMFGM)supplementation on ASD model mice.Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM.Behavioral results indicated MFGMs ameliorated social deficits,with GMFGM being more effective.Milk fat globule membrane(MFGM)mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression,meanwhile GMFGM increased the anti-inflammatory factor interleukin(IL)-10.MFGMs also altered gut microbiota composition and maintained gut barrier integrity.Uniquely,GMFGM increased butyrate production.Correlation analysis revealed positive associations between social behavior,levels of phosphatidylcholine,sphingomyelin,and the abundance of Allobaculum,Clostridium_sensu_stricto,and Turicibacter.Overall,these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.展开更多
BACKGROUND Autism spectrum disorders(ASD)represent a substantial social problem affecting at least 1 in 100 children worldwide.These conditions are very often accompanied by intellectual disability(ID)and speech delay...BACKGROUND Autism spectrum disorders(ASD)represent a substantial social problem affecting at least 1 in 100 children worldwide.These conditions are very often accompanied by intellectual disability(ID)and speech delay;thus,they can be considered within a clinical continuum of neurodevelopmental disorders.Given the high heterogeneity of ASD,the subjective nature of diagnostic criteria,and the presence of phenocopies,identifying genetic determinants of these disorders remains a challenge.AIM To investigate the spectrum and frequency of rare genetic variants in genes with proven association with ASD in Russian children.METHODS 110 patients from 106 families were recruited into the study mean age at diagnosis 6 years;boy-to-girl ratio 3:1.Most of the patients(84%)demonstrated a combination of ASD with developmental delay(DD)or ID.Patients with syndromic features were subjected to the chromosomal microarray analysis.The remained children underwent clinical exome sequencing aimed at identifying presumably monogenic causes of ASD.The study focused on rare(minor allele frequency≤0.001)variants affecting high-confidence ASD-associated genes.RESULTS Pathogenic copy number variations were detected in three(7%)of the patients examined.Clinical exome sequencing revealed pathogenic/likely pathogenic variants in 12 of 105 cases(11%),indicating the presence of monogenic syndromes with established clinical significance(Pitt-Hopkins syndrome,ZTTK syndrome,syndromic X-linked ID of Billuart type,Snijders-Blok-Campeau,Helsmoortel-van der Aa,Coffin-Siris,Clark-Baraitser,Keefstra syndromes,etc.).In addition,27 patients(26%)had 37 rare variants of unknown clinical significance in DSCAM,SHANK2,AUTS2,ADNP,ANKRD11,APBA2,ARID1B,ASTN2,ATRX,SCN1A,CHD2,DEAF1,EHMT1,GRIN2B,NBEA,NR4A2,TRIO,TRIP12,POGZ,EP300,FOXP1,PCDH19,GRIN2A,NCKAP1,and CHD8 genes.No specific variant was detected more than once in unrelated patients.Among the genes with rare variants found in 2 or more patients were TRIP12(n=4),AUTS2(n=3),ARID1B(n=3),PCDH19(n=3),EP300(n=3),TRIO(n=2),ASTN2(n=2),EHMT1(n=2),and CHD2(n=2).Of note,5 male ASD/DD patients from 3 unrelated families had PCDH19 missense variants,confirming that at least some hemizygous males with non-mosaic PCDH19 variants may present with neurobehavioral abnormalities.These variants did not cause epilepsy restricted to females in patients’mothers or sisters.CONCLUSION These data confirm a tremendous diversity of genetic causes of ASD.Clinical exome sequencing may serve as a reasonable alternative to whole-exome sequencing.展开更多
Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with ...Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes,but the underlying mechanisms are not fully understood.Here,we report that deletion of Trio,a high-susceptibility gene of ASDs,causes a postnatal dentate gyrus(DG)hypoplasia with a zigzagged suprapyramidal blade,and the Trio-defcient mice display autism-like behaviors.The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells(GCs),which further results in a migration defcit of neural progenitors.Furthermore,we reveal that Trio plays diferent roles in various excitatory neural cells by spatial transcriptomic sequencing,especially the role of regulating the migration of postmitotic GCs.In summary,our fndings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.展开更多
文摘Background: In Italy, there is a lack of reliable data on the epidemiology of Autism Spectrum Disorder (ASD) on a national scale. The exact etiopathogenesis of ASDs is still largely unknown, with autism representing the final common pathway of different pathological conditions. Aim of the Study: Assessment of the effects produced by the individualised, intensive and holistic rehabilitation programme used by the Il Cireneo Foundation on the daily living skills of people diagnosed with ASD. Materials and Methods: Out of the eighty-seven (n = 87) enrolees, seventy-nine (n = 79), of whom 19 were females (24.1%) and 60 were males (75.9%), with a mean age of 13.41 years (SD = 6.93 years;range = 2 - 33 years) terminated the three-year study. The enrolees were evaluated two times: at the beginning of the rehabilitation programme and at the end of the three-year goal-oriented project. Results: Statistically significant results between T0 and T1 were recorded for CARS (t-4.221;p Conclusions: People diagnosed with autism can be helped to become more autonomous and independent in carrying out activities of daily living thanks to an intensive psycho-educational and cognitive-behavioural rehabilitation programme, of which the Il Cireneo Foundation is the only expression in the Abruzzo region.
文摘BACKGROUND Managing critical care emergencies in children with autism spectrum disorder(ASD)presents unique challenges due to their distinct sensory sensitivities,communication difficulties,and behavioral issues.Effective strategies and protocols are essential for optimal care in these high-stress situations.AIM To systematically evaluate and synthesize current evidence on best practices for managing critical care emergencies in children with ASD.The review focuses on key areas,including sensory-friendly environments,communication strategies,behavioral management,and the role of multidisciplinary approaches.METHODS A comprehensive search was conducted across major medical databases,including PubMed,Embase,and Cochrane Library,for studies published between 2000 and 2023.Studies were selected based on their relevance to critical care management in children with ASD,encompassing randomized controlled trials,observational studies,qualitative research,and case studies.Data were extracted and analyzed to identify common themes,successful strategies,and areas for improvement.RESULTS The review identified 50 studies that met the inclusion criteria.Findings highlighted the importance of creating sensory-friendly environments,utilizing effective communication strategies,and implementing individualized behavioral management plans.These findings,derived from a comprehensive review of current evidence,provide valuable insights into the best practices for managing critical care emergencies in children with ASD.Sensory modifications,such as reduced lighting and noise,visual aids,and augmentative and alternative communication tools,enhanced patient comfort and cooperation.The involvement of multidisciplinary teams was crucial in delivering holistic care.Case studies provided practical insights and underscored the need for continuous refi-nement of protocols.CONCLUSION The review emphasizes the need for a tailored approach to managing critical care emergencies for children with ASD.Sensory-friendly adjustments,effective communication,and behavioral strategies supported by a mul-tidisciplinary team are integral to improving outcomes.Despite progress,ongoing refinement of care practices and protocols is necessary.This ongoing process addresses remaining challenges and engages healthcare professionals in continuous improvement of care for children with ASD in critical settings.
文摘We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.
文摘Objective Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by difficulties with communication and social interaction,restricted and repetitive behaviors.Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits,which are closely related to the core symptoms of ASD.Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities.Therefore,this study explores the behavior of children with ASD in capturing attention to changes in topological properties.Methods Our study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing(TD)age-matched controls.In an attention capture task,we recorded the saccadic behaviors of children with ASD and TD in response to topological change(TC)and non-topological change(nTC)stimuli.Saccadic reaction time(SRT),visual search time(VS),and first fixation dwell time(FFDT)were used as indicators of attentional bias.Pearson correlation tests between the clinical assessment scales and attentional bias were conducted.Results This study found that TD children had significantly faster SRT(P<0.05)and VS(P<0.05)for the TC stimuli compared to the nTC stimuli,while the children with ASD did not exhibit significant differences in either measure(P>0.05).Additionally,ASD children demonstrated significantly less attention towards the TC targets(measured by FFDT),in comparison to TD children(P<0.05).Furthermore,ASD children exhibited a significant negative linear correlation between their attentional bias(measured by VS)and their scores on the compulsive subscale(P<0.05).Conclusion The results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection.This atypical attention may affect the child’s cognitive and behavioral development,thereby impacting their social communication and interaction.In sum,our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.
文摘Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.
文摘This article describes a pilot study aiming at generating social interactions between a humanoid robot and adolescents with autism spectrum disorder (ASD), through the practice of a gesture imitation game. The participants were a 17-year-old young lady with ASD and intellectual deficit, and a control participant: a preadolescent with ASD but no intellectual deficit (Asperger syndrome). The game is comprised of four phases: greetings, pairing, imitation, and closing. Field educators were involved, playing specific roles: visual or physical inciter. The use of a robot allows for catching the participants’ attention, playing the imitation game for a longer period of time than with a human partner, and preventing the game partner’s negative facial expressions resulting from tiredness, impatience, or boredom. The participants’ behavior was observed in terms of initial approach towards the robot, positioning relative to the robot in terms of distance and orientation, reactions to the robot’s voice or moves, signs of happiness, and imitation attempts. Results suggest a more and more natural approach towards the robot during the sessions, as well as a higher level of social interaction, based on the variations of the parameters listed above. We use these preliminary results to draw the next steps of our research work as well as identify further perspectives, with this aim in mind: improving social interactions with adolescents with ASD and intellectual deficit, allowing for better integration of these people into our societies.
文摘BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental disorder that manifests in the first years of life,with a complex pathogenesis influenced by biological,genetic and epigenetic factors.Many children with ASD display marked food selectivity,often restricting themselves to a narrow range of foods.The problems associated with feeding children with ASD can vary widely,from mild cases that pose no immediate health risks,to more severe situations with a risk of mal-nutrition or,conversely,overeating.This scoping review aims to provide an in-depth overview of the frequency,nature and factors related to food selectivity in children with autism.AIM To comprehensively review the literature on food selectivity in ASD.METHODS A systematic review of the literature was conducted using the PubMed,Web of Science and EBSCO databases,to identify articles published in English from 2014 until 2024.Studies on a sample diagnosed with ASD and food selectivity were included.The selected databases were chosen for their broad coverage of the scientific literature.These databases represent reliable sources of high-quality articles,ensuring a comprehensive and up-to-date search.RESULTS We evaluated 222 studies on food selectivity in autism,from which duplicates were removed and unrelated titles were filtered out.Finally,9 articles were included in the review.Five articles provide a general overview of the phenomenon,analysing its nature and factors.Two studies delve into sensory sensitivity,in particular the impact of food textures,tastes and smells.Finally,two studies focus on problem behaviour during mealtimes.CONCLUSION Children with ASD have greater food selectivity than the neurotypical population.The diet should contain a greater variety of fruit,vegetables,yoghurt,while reducing the consumption of rice and pasta.
基金supported by grants from the National Natural Science Foundation of China(82125032,81930095,82204048 and 81761128035)the Science and Technology Commission of Shanghai Municipality(19410713500 and 2018SHZDZX01)+3 种基金the Foundation of Shanghai Municipal Commission of Health and Family Planning(GWV-10.1-XK07,2020CXJQ01 and 2018YJRC03)the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20211100)the Guangdong Key Project(2018B030335001).
文摘To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial magnetic stimulation(rTMS),one of the most commonly applied non-invasive neurostimulation techniques,has shown efficacy in treating neuropsychiatric disorders,such as depression.
文摘Autism spectrum disorder(ASD)is an early-onset neurodevelopmental disorder marked by persistent deficits in social communication and interaction,alongside restricted,repetitive patterns of behaviors(RRB),interests,or activities.It often co-occurs with various neuropsychiatric disorders,though their frequency varies widely due to unclear boundaries between the core features of ASD and common comorbidities.Catatonia,increasingly noted in neurodevelopmental conditions like ASD,shares striking similarities with ASD in symptomatology,brain mech-anisms,and treatment responses,prompting the question of whether it is a core feature of ASD or a distinct condition.This paper delved into this overlap,ex-ploring the relationship between catatonia and ASD through a narrative review of peer-reviewed literature from 1943 to 2024,sourced from PubMed and psy-chiatric journals.Focusing on ASD diagnostic evolution,symptom overlap with catatonia,and shared neurobiological and therapeutic characteristics,we used thematic analysis to synthesize findings into key areas such as historical nosology,phenomenological overlap,neurobiological parallels,and treatment response.The evidence revealed weak support for separating catatonia from overlapping RRB features of ASD,suggesting that some RRB might align more with comorbid catatonia than intrinsic ASD traits.However,this idea needs further validation through rigorous clinical trials.Clarifying this relationship could refine diagnostic approaches and open doors to targeted treatments,potentially improving out-comes for those affected.
文摘The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide.Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via heavy metal exposures and nutritional deficits that impact the expression of genes.In the case of the metallothionein(MT)gene,biomarker studies show dietary zinc(Zn)deficits impact MT protein levels in children with autism and are associated with the bioaccumulation of lead and/or mercury in children exhibiting autism/attention deficit/hyperactivity disorders symptomology.The impact of dietary changes on lead and mercury exposures and MT gene behavior could be determined using a randomized test and control group design.Pregnant women serving in the testgroup would participate in a nutritional epigenetics education intervention/course designed to reduce ultra-processed food intake and heavy metal levels in blood while increasing whole food intake and MT and Zn levels.Changes in maternal diet would be measured using data derived from an online diet survey administered to the test and control groups pre-post intervention.Changes in maternal lead,mercury,Zn,and MT levels would be measured via blood sample analyses prior to the intervention and after childbirth via cord blood analyses to determine infant risk factors.
基金Supported by the National Key Research and Development Program of China,No.2024YFC2707801the Science and Technology Innovation Commission of Shenzhen,No.JCYJ20230807143800002.
文摘BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.
文摘Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psychiatric,and behavioral issues,highlighting the urgent need for autism-competent healthcare providers in general healthcare.This review aims to equip primary care providers(PCPs)with a concise summary of common CCs and strategies for effective identification.A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature,research evidence,and existing clinical trial outcomes,supplementing their clinical expertise.Autistic children consistently show higher rates of both medical and mental health issues.Despite greater healthcare utilization,many autistic individuals report unmet needs.CCs can impair behavior,functioning,and well-being,but are often treatable when recognized early.Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families.This evidence-based review supports PCPs in enhancing their knowledge,fostering early recognition,and delivering comprehensive,responsive care.
基金supported by the Humanities and Social Sciences Research Planning Fund of Chinese Ministry of Education(22YJAZH150).
文摘Background:Parents of children with autism are susceptible to parenting burnout due to tremendous parenting burden and parenting challenges.Parenting burnout has a detrimental effect on both children with autism and their parents.However,the underlying mechanisms that lead to parenting burnout remain unclear.This study aimed to investigate the relationship between parenting stress and parenting burnout,along with the serial mediation effect of social support and coping strategies in the context of families with autistic children.Methods:We conducted a cross-sectional study in 231 parents of autistic children in four autism facilities located in central Hubei province.Data were collected through the Parental Stress Index,Social Support Rating Scale,Simplified Coping Strategies Questionnaire,and Caregiver Burnout Assessment Questionnaire.Results:Parenting stress and burnout status were:72.3%of parents reported high-stress levels,16.9%experienced risks for parenting burnout,and 19.9%were currently experiencing burnout.Both social support and coping strategies played partial mediating roles in the relationship between parental stress and burnout,forming a serial mediation effect.Conclusion:Parenting stress is a risk factor for parenting burnout.Social support and coping strategies play a chain mediating role between parenting stress and parenting burnout,which may act as the underlying mechanisms.The study offers insights into potential intervention points for reducing parenting burnout.Future efforts are needed to devote to parenting stress,social support and coping strategy to enhance the psychological well-being of parents with autistic children.
基金Supported by Lanzhou Philosophy and Social Science Planning Project,No.24-B13the Youth Project of Philosophy and Social Science Foundation of Gansu Province,No.2024QN015the General Project of Philosophy and Social Science Foundation of Gansu Province,No.2024YB049.
文摘Autism spectrum disorder(ASD)poses significant challenges for families,with limited access to specialized care being a critical concern.The coronavirus disease 2019 pandemic has accelerated the adoption of remote support,highlighting its potential to enhance family-centered care for children with ASD.In this editorial,we comment on the article by Lu et al,emphasizing the effectiveness of integrating remote support courses with traditional caregiver-mediated interventions.We further explore the benefits of remote support in delivering family-centered care,summarize the essential components of effective family-centered remote support,outline key considerations for implementation,and discuss potential future research directions.We conclude that family-centered remote support has the potential to significantly improve outcomes and quality of life for individuals with ASD and their families.
基金Supported by Jiangsu Department of Science and Technology Key R&D Program(No.BE2023777)the Jiangsu Commission of Health(No.H2022185)Jiangsu Province Hospital(the First Affiliated Hospital of Nanjing Medical University)Clinical Capacity Enhancement Project(No.JSPH-MB-2023-18).
文摘Autism spectrum disorder(ASD)represents a neurodevelopmental disorder that has been the focus of numerous studies on the central nervous system(CNS).The embryological origin of the brain and retina is shared,with the axons of retinal ganglion cells(RGC)developing into the optic nerves that enter the brain through the dorsal lateral geniculate nucleus(LGN)of the thalamus,LGN,and other visual cortices.Given the evidence that individuals with ASD exhibit impairments in the visual mechanisms,including deficits in emotional face recognition,and difficulty in maintaining gaze control as well as eye contact,some studies have documented retinal alterations in individuals with ASD.These have been identified through ophthalmic assessments,including optical coherence tomography(OCT),optical coherence tomography angiography(OCTA),and electroretinography(ERG).With the improvements in ASD animal models,it is possible to obtain a better understanding of vision dysfunction in ASD by analyzing the molecular mechanisms of retinal function and structure abnormalities.This review aims to provide a summary of the recent research on ocular alterations in ASD patients and animal models,intending to contribute to further investigation of the eye-brain connection and communication.
文摘One of the core challenges faced by children with autism is repetitive motor behavior,which not only undermines their learning efficiency in the classroom but also makes it difficult for them to integrate smoothly into inclusive educational settings,thereby hindering their social adaptation and overall development.This study adopted a single-case design focusing on a first-grade student with autism enrolled in a mainstream class at Xiangxue Primary School,Huangpu District,Guangzhou.Functional behavior assessment was conducted to systematically observe and analyze the student’s repetitive motor behaviors in class,on the basis of which an intervention plan was developed and implemented.The intervention incorporated antecedent control,replacement behavior training,and consequence management,supplemented by collaboration between school and family.The findings indicated that the frequency of repetitive motor behaviors decreased significantly after the intervention,while the student demonstrated improved classroom participation and peer interaction;these positive effects were maintained during the follow-up phase.The study suggests that in inclusive education settings,interventions guided by functional behavior assessment can effectively reduce problem behaviors in children with autism and enhance their classroom engagement and learning adaptability.
基金supported by the Central Government Guidance Local Science and Technology Development Fund Project(2021Szvup119)the Key Research and Development Plan of Shaanxi Province(2023-YBNY-184)+3 种基金the Regional Consolidated Fund-Youth Fund Project in Guangdong Province(2022A1515110717)China Postdoctoral Science Foundation(2022M72261)Guangdong Basic and Applied Basic Research Foundation(2021A1515110813)the 2021-National Center of Technology Innovation for Dairy-5.
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule membrane(GMFGM)supplementation on ASD model mice.Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM.Behavioral results indicated MFGMs ameliorated social deficits,with GMFGM being more effective.Milk fat globule membrane(MFGM)mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression,meanwhile GMFGM increased the anti-inflammatory factor interleukin(IL)-10.MFGMs also altered gut microbiota composition and maintained gut barrier integrity.Uniquely,GMFGM increased butyrate production.Correlation analysis revealed positive associations between social behavior,levels of phosphatidylcholine,sphingomyelin,and the abundance of Allobaculum,Clostridium_sensu_stricto,and Turicibacter.Overall,these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.
基金Supported by the Russian Science Foundation Grant,No.24-45-00067.
文摘BACKGROUND Autism spectrum disorders(ASD)represent a substantial social problem affecting at least 1 in 100 children worldwide.These conditions are very often accompanied by intellectual disability(ID)and speech delay;thus,they can be considered within a clinical continuum of neurodevelopmental disorders.Given the high heterogeneity of ASD,the subjective nature of diagnostic criteria,and the presence of phenocopies,identifying genetic determinants of these disorders remains a challenge.AIM To investigate the spectrum and frequency of rare genetic variants in genes with proven association with ASD in Russian children.METHODS 110 patients from 106 families were recruited into the study mean age at diagnosis 6 years;boy-to-girl ratio 3:1.Most of the patients(84%)demonstrated a combination of ASD with developmental delay(DD)or ID.Patients with syndromic features were subjected to the chromosomal microarray analysis.The remained children underwent clinical exome sequencing aimed at identifying presumably monogenic causes of ASD.The study focused on rare(minor allele frequency≤0.001)variants affecting high-confidence ASD-associated genes.RESULTS Pathogenic copy number variations were detected in three(7%)of the patients examined.Clinical exome sequencing revealed pathogenic/likely pathogenic variants in 12 of 105 cases(11%),indicating the presence of monogenic syndromes with established clinical significance(Pitt-Hopkins syndrome,ZTTK syndrome,syndromic X-linked ID of Billuart type,Snijders-Blok-Campeau,Helsmoortel-van der Aa,Coffin-Siris,Clark-Baraitser,Keefstra syndromes,etc.).In addition,27 patients(26%)had 37 rare variants of unknown clinical significance in DSCAM,SHANK2,AUTS2,ADNP,ANKRD11,APBA2,ARID1B,ASTN2,ATRX,SCN1A,CHD2,DEAF1,EHMT1,GRIN2B,NBEA,NR4A2,TRIO,TRIP12,POGZ,EP300,FOXP1,PCDH19,GRIN2A,NCKAP1,and CHD8 genes.No specific variant was detected more than once in unrelated patients.Among the genes with rare variants found in 2 or more patients were TRIP12(n=4),AUTS2(n=3),ARID1B(n=3),PCDH19(n=3),EP300(n=3),TRIO(n=2),ASTN2(n=2),EHMT1(n=2),and CHD2(n=2).Of note,5 male ASD/DD patients from 3 unrelated families had PCDH19 missense variants,confirming that at least some hemizygous males with non-mosaic PCDH19 variants may present with neurobehavioral abnormalities.These variants did not cause epilepsy restricted to females in patients’mothers or sisters.CONCLUSION These data confirm a tremendous diversity of genetic causes of ASD.Clinical exome sequencing may serve as a reasonable alternative to whole-exome sequencing.
基金supported by grants from the Key Realm R&D Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(82071541,81971283,82271576,and 82101570)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT320-08).
文摘Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes,but the underlying mechanisms are not fully understood.Here,we report that deletion of Trio,a high-susceptibility gene of ASDs,causes a postnatal dentate gyrus(DG)hypoplasia with a zigzagged suprapyramidal blade,and the Trio-defcient mice display autism-like behaviors.The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells(GCs),which further results in a migration defcit of neural progenitors.Furthermore,we reveal that Trio plays diferent roles in various excitatory neural cells by spatial transcriptomic sequencing,especially the role of regulating the migration of postmitotic GCs.In summary,our fndings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
