Etiology Of Autism Spectrum Disorder Research Articles

Is autism spectrum disorder an inflammation?

<p>In our study, we aimed to evaluate inflammation by measuring serum Adenosine deaminase and dipeptidyl peptidase IV levels of individuals diagnosed with autism spectrum disorder and to determine its relationship with the Childhood Autism Rating Scale.</p>. <p>37 children aged 2-12 years with a diagnosis of autism spectrum disorder and 27 children aged 2-12 years without any psychiatric disease were included in the study. Psychiatric examination and clinical evaluation according to DSM-5 diagnostic criteria for the diagnosis of autism spectrum disorder were performed on the children included in the study. The Childhood Autism Rating Scale was filled in by the researcher by interviewing the parents of the children diagnosed with autism spectrum disorder. 5 ml of venous blood samples were taken from the children in both groups in the morning on a full stomach.</p>. <p>There was no statistically significant difference between the groups in terms of age, gender, and sociodemographic data. While serum adenosine deaminase levels were found to be statistically significantly higher in the group with autism spectrum disorder, serum dipeptidyl peptidase IV levels were found to be significantly lower. A positive correlation was found between dipeptidyl peptidase IV and Childhood Autism Rating Scale.</p>. <p>We think that inflammation may play a role in the etiology of autism spectrum disorder due to altered adenosine deaminase and dipeptidyl peptidase IV levels in children with autism spectrum disorder.</p>.

Copy Number Variation Informs fMRI-based Prediction of Autism Spectrum Disorder.

The multifactorial etiology of autism spectrum disorder (ASD) suggests that its study would benefit greatly from multimodal approaches that combine data from widely varying platforms, e.g., neuroimaging, genetics, and clinical characterization. Prior neuroimaging-genetic analyses often apply naive feature concatenation approaches in data-driven work or use the findings from one modality to guide posthoc analysis of another, missing the opportunity to analyze the paired multimodal data in a truly unified approach. In this paper, we develop a more integrative model for combining genetic, demographic, and neuroimaging data. Inspired by the influence of genotype on phenotype, we propose using an attention-based approach where the genetic data guides attention to neuroimaging features of importance for model prediction. The genetic data is derived from copy number variation parameters, while the neuroimaging data is from functional magnetic resonance imaging. We evaluate the proposed approach on ASD classification and severity prediction tasks, using a sex-balanced dataset of 228 ASD and typically developing subjects in a 10-fold cross-validation framework. We demonstrate that our attention-based model combining genetic information, demographic data, and functional magnetic resonance imaging results in superior prediction performance compared to other multimodal approaches.

The Promise of Personalized &amp; Precision Genomics in Autism

Despite recent advances in understanding the etiology of autism spectrum disorder (ASD), an approved and efficacious treatment strategy has yet to be identified. The latter demonstrates that the canonical ASD profiled care is becoming much less beneficial and productive, yet it remains ineffective in preventing or effectively treating the above-mentioned disorder. Meanwhile, the link that might exert reliable control over morbidity, mortality and disabling rates as well as significantly optimize the efficacy of ASD treatment for those who had fallen ill and for persons-atrisk is Personalized &amp; Precision Medicine (PPM). Recent advances in ASD genetics pave the way for implementation of PPM in clinical management of autism. Thus, identification of gene modifiers and epigenetic, transcriptional, and translational regulators of implicated genes is important for a more complete understanding of the genetic risk and the precise roles of specific variants. The inherent complexity and heterogeneity of ASD, often further complicated by comorbid sleep disturbances, epilepsy, or attention deficit hyperactivity disorder (ADHD), has been a prominent impediment to achieving a well-defined treatment algorithm. However, the protocols of symptomatic treatment are not considered in this article, since they have been known for a long time and do not reveal the ideology of personalized targeted therapy. In this review, we have accumulated the latest data from the main areas of pathogenetic target discovery using PPM-based tools and omics technologies, in particular genomics, which hold great promise for the development of personalized preventive diagnostic and therapeutic protocols.

Shared and divergent contribution of vitamin A and oxytocin to the aetiology of autism spectrum disorder

Rare genetic variations contribute to the heterogeneity of autism spectrum disorder (ASD) and the responses to various interventions for ASD probands. However, the associated molecular underpinnings remain unclear. Herein, we estimated the association between rare genetic variations in 410 vitamin A (VA)-related genes (VARGs) and ASD aetiology using publicly available de novo mutations (DNMs), rare inherited variants, and copy number variations (CNVs) from about 50,000 ASD probands and 20,000 normal controls (discovery and validation cohorts). Additionally, given the functional relevance of VA and oxytocin, we systematically compared the similarities and differences between VA and oxytocin with respect to ASD aetiology and evaluated their potential for clinical applications. Functional DNMs and pathogenic CNVs in VARGs contributed to ASD pathogenesis in the discovery and validation cohorts. Additionally, 324 potential VA-related biomarkers were identified, 243 of which were shared with previously identified oxytocin-related biomarkers, while 81 were unique VA biomarkers. Moreover, multivariable logistic regression analysis revealed that both VA- and oxytocin-related biomarkers were able to predict ASD aetiology for individuals carrying functional DNM in corresponding biomarkers with an average precision of 0.94. As well as, convergent and divergent functions were also identified between VA- and oxytocin-related biomarkers. The findings of this study provide a basis for future studies aimed at understanding the pathophysiological mechanisms underlying ASD while also defining a set of potential molecular biomarkers for adjuvant diagnosis and intervention in ASD.

Associação entre o transtorno do espectro do autismo e eventos periparto: estudo de caso-controle

Objective:To assess the association between peripartum events and autism spectrum disorder (ASD) development in children and adolescents.Methods:The current research is a case–control study in northern Minas Gerais state, Brazil. The inclusion criteria in the case group included individuals whose medical records reported an autistic disorder diagnosis, individuals had this diagnosis further confirmed by Northern Minas Autistic Support Association and specialized clinics, and their mothers had to answer positively to the question: “Was your child diagnosed with autism spectrum disorder?” in the data collection instrument. Thus, the case group included 253 mothers of children/adolescents of 2–15 years old diagnosed with autism. The inclusion criteria in the control group included 852 individuals belonging to the same age group and enrolled in the same schools as the case group. A semi-structured questionnaire was applied for mothers of children/adolescents, and the multiple logistic regression model was adopted for data analysis. Gross and adjusted Odds Ratios (ORa) were used to estimate the magnitude of the associations.Results:Autistic disorder was associated with the presence of meconium in amniotic fluid (AF) (ORa 1.67; 95% confidence interval [95%CI] 1.06–2.65) and cesarean delivery type (ORa 1.65; 95%CI 1.17–2.32). Emergency cesarean section increased autistic disorder development likelihood (ORa 2.38; 95%CI 1.61–3.51). Children and adolescents with ASD were more likely to have been exposed to two or more unfavorable peripartum events and obstetric complications than control groups (ORa 1.59; 95%CI 1.01–2.51).Conclusions:Meconium stained amniotic fluid, delivery by cesarean, and two or more unfavorable peripartum events are variables that should be considered in studies about ASD etiology.

Autism spectrum disorder: Current progress in therapeutic options for mitochondrial dysfunction and ongoing management possibilities with a multifariousness: A critical overviewAutism spectrum disorder: Current progress in therapeutic options for mitochon

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in interactions, social skills and communications. It consists of an inability to acquire social and emotional skills during early developmental age that to one to two years of the age which progressively results in variable degrees of social adaptation incapacity. Over the last 20 years, the frequency of ASD has progressively increased, with a recent estimate about 1 in 36 children and with boys 4 times more susceptible to the development of ASD than girls. The etiology of ASD is multifactorial and includes functional and structural neurological abnormalities. There is an alarming lack of knowledge in the subject among health care professionals. Hence it is needed to be aware of the people and manages aggressive behavior, hyperactivity, and irritability. Past two decades many efforts have focused on the determination of genes associated with autism, immune dysfunction and free radicles contributing to ASD. The present article aims to highlight the current state knowledge regarding the role of mitochondrial DNA (mtDNA) in the etiology of ASD, core symptoms, diagnosis, therapeutic aspects (meditational and non-meditational) and the prediction of clinical outcomes in the future.

Independent and Combined Effects of Probiotics and Prebiotics as Supplements or Food-Rich Diets on a Propionic-Acid-Induced Rodent Model of Autism Spectrum Disorder.

The link between nutrition and autism spectrum disorder (ASD) as a neurodevelopmental condition, which is clinically presented as significant delays or deviations in interaction and communication, has provided a fresh point of view and signals that nutrition may play a role in the etiology of ASD, as well as playing an effective role in treatment by improving symptoms. In this study, 36 male albino rat pups were used. They were randomly divided into five groups. The control group was fed only a standard diet and water for the 30 days of the experiment. The second group, which served as a propionic acid (PPA)-induced rodent model of ASD, received orally administered PPA (250 mg/kg body weight (BW)) for 3 days, followed by feeding with a standard diet until the end of the experiment. The three other groups were given PPA (250 mg/kg body weight (BW)) for 3 days and then fed a standard diet and orally administered yogurt (3 mL/kg BW/day), artichokes (400 mL/kg BW/day), and a combination of Lacticaseibacillus rhamnosus GG at 0.2 mL daily (1 × 109 CFU; as the probiotic of yogurt) and luteolin (50 mg/kg BW/day; as the major antioxidant and anti-inflammatory ingredient of artichokes) for 27 days. Biochemical markers, including gamma-aminobutyric acid (GABA), reduced glutathione (GSH), glutathione peroxidase (GPx1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured in brain homogenates in all groups. The data showed that while PPA demonstrated oxidative stress and neuroinflammation in the treated rats, yogurt, Lacticaseibacillus rhamnosus GG as a probiotic, and luteolin as a prebiotic ingredient in artichokes were effective in alleviating the biochemical features of ASD. In conclusion, nutritional supplementation seems to be a promising intervention strategy for ASD. A combined dietary approach using pro- and prebiotics resulted in significant amelioration of most of the measured variables, suggesting that multiple interventions might be more relevant for the improvement of biochemical autistic features, as well as psychological traits. Prospective controlled trials are needed before recommendations can be made regarding the ideal ASD diet.

WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.

Do Parental Comorbidities Affect the Severity of Autism Spectrum Disorder?

Background Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by defective social communication and interaction with a repetitive pattern of monotonous or stereotyped behavior.Although the exact etiology of ASD is unknown, many factors may be implicated in the development of ASD.We aimed to determine the correlation between specific parental factors and Autism Treatment Evaluation Checklist (ATEC) scores. Methods This cross-sectional study was conducted at the Prince Nasser Bin Abdulaziz Center for Autism, Autism Center for Excellence, and Academy of Special Education for Autism in Riyadh, Saudi Arabia. We enrolled children diagnosed with ASD and their parents from these centers. Data were collected through self-administered questionnaires to the patients' parents. Results All included children were <18 years old. In total, 71 (92.2%) children were male and six (7.8%) were female. Further, 77 (100%) patients were diagnosed with autistic disorder. Children of consanguineous parents, underweight mothers and obese fathers, mothers with a history of depression during pregnancy, and mothers aged ≥31 years during pregnancy tend to have a higher mean ATEC score. The health domain was the most significantly correlated with ATEC scores, with a Pearson correlation of 0.880. In linear regression analysis, only maternal depression during pregnancy was significantly correlated with ATEC scores. Conclusion Our patients had a mean ATEC score of 86.2. The health domain was the most significantly correlated with ATEC scores, with a Pearson correlation of 0.880. Linear regression analysis revealed that consanguinity, parental chronic disease, parental allergy, smoking, druguse during pregnancy, paternal and maternal body mass index (BMI), and siblingnumber were not significantly correlated with ATEC scores (P=0.701, 0.693, 0.133, 0.874, 0.982, 0.255, 0.778, and 0.502, respectively). However, maternal depression during pregnancy was significantly correlated with ATEC scores (P=0.055).

Novel correlative analysis identifies multiple genomic variations impacting ASD with macrocephaly.

Autism spectrum disorders (ASD) display both phenotypic and genetic heterogeneity, impeding the understanding of ASD and development of effective means of diagnosis and potential treatments. Genes affected by genomic variations for ASD converge in dozens of gene ontologies (GOs), but the relationship between the variations at the GO level have not been well elucidated. In the current study, multiple types of genomic variations were mapped to GOs and correlations among GOs were measured in ASD and control samples. Several ASD-unique GO correlations were found, suggesting the importance of co-occurrence of genomic variations in genes from different functional categories in ASD etiology. Combined with experimental data, several variations related to WNT signaling, neuron development, synapse morphology/function and organ morphogenesis were found to be important for ASD with macrocephaly, and novel co-occurrence patterns of them in ASD patients were found. Furthermore, we applied this gene ontology correlation analysis method to find genomic variations that contribute to ASD etiology in combination with changes in gene expression and transcription factor binding, providing novel insights into ASD with macrocephaly and a new methodology for the analysis of genomic variation.

Gene editing in monogenic autism spectrum disorder: animal models and gene therapies.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disease, and its diagnosis is dependent on behavioral manifestation, such as impaired reciprocal social interactions, stereotyped repetitive behaviors, as well as restricted interests. However, ASD etiology has eluded researchers to date. In the past decades, based on strong genetic evidence including mutations in a single gene, gene editing technology has become an essential tool for exploring the pathogenetic mechanisms of ASD via constructing genetically modified animal models which validates the casual relationship between genetic risk factors and the development of ASD, thus contributing to developing ideal candidates for gene therapies. The present review discusses the progress in gene editing techniques and genetic research, animal models established by gene editing, as well as gene therapies in ASD. Future research should focus on improving the validity of animal models, and reliable DNA diagnostics and accurate prediction of the functional effects of the mutation will likely be equally crucial for the safe application of gene therapies.

Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Abnormal lipid metabolism has been suggested to contribute to its pathogenesis. Further exploration of its underlying biochemical mechanisms is needed. In a search for reliable biomarkers for the pathophysiology of ASD, hippocampal tissues from the ASD model BTBR T+ Itpr3tf/J (BTBR) mice and C57BL/6J mice were analyzed, using four-dimensional (4D) label-free proteomic analysis and bioinformatics analysis. Differentially expressed proteins were significantly enriched in lipid metabolic pathways. Among them, apolipoprotein A-I (ApoA-I) is a hub protein and its expression was significantly higher in the BTBR mice. The investigation of protein levels (using Western blotting) also confirmed this observation. Furthermore, expressions of SphK2 and S1P in the ApoA-I pathway both increased. Using the SphK inhibitor (SKI-II), ASD core phenotype and phenotype-related protein levels of P-CREB, P-CaMKII, and GAD1 were improved, as shown via behavioral and molecular biology experiments. Moreover, by using SKI-II, we found proteins related to the development and function of neuron synapses, including ERK, caspase-3, Bax, Bcl-2, CDK5 and KCNQ2 in BTBR mice, whose levels were restored to protein levels comparable to those in the controls. Elucidating the possible mechanism of ApoA-I in ASD-associated phenotypes will provide new ideas for studies on the etiology of ASD.

Fecal Microbiota Transplantation in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that begin in infancy. In recent years, the incidence of ASD in the world is increasing year by year. At present, the etiology and pathogenesis of ASD are not clear, and effective treatments are still lacking. In addition to neurobehavioral symptoms, children with ASD often have obvious gastrointestinal symptoms. Gut microbiota is a large microbial community in the human gut, which is closely related to the nervous system and can affect brain development and behavior through the neuroendocrine, neuroimmune and autonomic nervous systems, forming a microbiota-gut-brain axis connection. Recent studies have shown that children with ASD have significant gut microbiota and metabolic disorders, and fecal microbiota transplantation (FMT) is expected to improve ASD-related symptoms by regulating gut microbiota and metabolism. This review paper will therefore focus on FMT in the treatment of ASD, and FMT is effective in improving gastrointestinal and neurobehavioral symptoms in children with ASD.

УСИЛЕНИЕ ОКИСЛИТЕЛЬНОГО СТРЕССА, УРОВНЯ АПОПТОЗА И ИЗМЕНЕНИЕ В УРОВНЕ ЭКСПРЕССИИ ГЕННОВ BCL И BAX У ДЕТЕЙ С ТЯЖЕЛОЙ ФОРМОЙ РАС

Autism Spectrum Disorders (ASDs) are a heterogeneous group of psychiatric disorders most commonly seen in children. Patients with ASD are characterized by cognitive, behavioral, communicative deficits and obsessive stereotypical behavior. At that moment, the etiology and pathogenesis of ASD is one of the most important problems in child psychiatry. Patients with ASD are characterized by increased oxidative stress. The aim of this study was to characterize the role of oxidative stress in patients with ASD in enhancing the level of apoptosis. The clinical group consisted of 133 children with ASD (DSM-5), &#x0D; 4-12 years old, who were followed up by the Federal State Budget Scientific Institution National Center for Health Care. Children with ASD were divided into two subgroups according to the severity of the course of the disease, according to CARS scores. The control group included 27 healthy children. Lymphocytes were isolated from whole blood by centrifugation in a ficoll-urographin gradient. The level of gene expression in peripheral blood lymphocytes of patients with ASD and healthy controls was assessed by quantitative determination of the mRNA level by real-time PCR and by the level of protein in cells, flow cytometry. cytofluorometry. In the lymphocytes of children from the subgroup with mild and moderate forms of ASD, the level of ROS was increased, but the level of significance was not reached, while in the lymphocytes of children with severe ASD, the level of ROS was 2.2-2.5 times higher than in children of the control group. groups (p&lt;0.01). The level of expression of the anti-apoptotic gene BCL2 in lymphocytes of children with severe ASD was reduced by 2-2.5 times (p&lt;0.01), and the level of expression of the pro-apoptotic BAX gene was increased by 1.8-2.3 (p&lt;0.01) times higher compared to the control. This may indicate an increase in oxidative stress and apoptosis in patients with severe ASD.

The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice

Recent understanding of Autism Spectrum Disorder (ASD) showed that peripheral primary mechanosensitive neurons involved in touch sensation and central neurons affected in ASD share transcriptional regulators. Mutant mice for ASD-associated transcription factors exhibit impaired primary tactile perception and restoring those genes specifically in primary sensory neurons rescues some of the anxiety-like behavior and social interaction defects. Interestingly, peripheral mechanosensitive sensory neurons also project to internal organs including the cardiovascular system, and an imbalance of the cardio-vascular sympathovagal regulation is evidenced in ASD and intellectual disability. ASD patients have decreased vagal tone, suggesting dysfunction of sensory neurons involved in cardio-vascular sensing. In light of our previous finding that the ASD-associated Meis2 gene is necessary for normal touch neuron development and function, we investigated here if its inactivation in mouse peripheral sensory neurons also affects cardio-vascular sympathovagal regulation and baroreflex. Combining echocardiography, pharmacological challenge, blood pressure monitoring, and heart rate variability analysis, we found that Meis2 mutant mice exhibited a blunted vagal response independently of any apparent cardiac malformation. These results suggest that defects in primary sensory neurons with mechanosensitive identity could participate in the imbalanced cardio-vascular sympathovagal tone found in ASD patients, reinforcing current hypotheses on the role of primary sensory neurons in the etiology of ASD.

Chemical Induced Rodent Model of Autism Spectrum Disorders

The term Autism spectrum disorder (ASD) refers to a neuro-developmental disorder that include repetitive behaviours, extremely constrained interests and deficits in social communication. In the last ten years, the numerous epidemiological papers discussing connection between autism and environmental chemical exposures has significantly increased. These findings are crucial because they focus on modifiable risk factors that may open up new possibilities for the primary prevention of the autism-related disability, which is now recognised to be more strongly related to environmental factors than was previously thought. A variety of environmental factors have been known as significant factors relevant to aetiology of ASD, such as lead and mercury (heavy metals), PCB(organic contaminant) and phthalates and BPA. The most accurate animal model of autism among all other models is valproic acid-induced autism, which can reproduce almost all of the molecular and cellular changes seen in humans with ASD. This review provide insight into various diagnostic available for autism, pathophysiology of autism and animal model of autism to develop a pharmacological therapeutic intervention for the treatment of disease.

Interstitial Duplication on Chromosome 3p14.3p13 in an Adolescent with Dysmorphic Features and Autism, Case Report

Abstract Introduction/Objective The genetic etiology of autism spectrum disorders is only partially understood. Here we describe a 16-year-old male diagnosed with autism at two years of age. He has dysmorphic features, severe cognitive disability, and history of cryptorchidism. A review of systems was significant for slightly coarse features overall, with deep-set eyes, pinched nasal bridge with wide nasal tip, and widely spaced teeth. A large pectus excavatum deformity was also noted. Although the parent’s genetic testing concluded that this likely represents de novo mutation, it is worth mentioning that our patient has a 13-year-old female maternal first cousin with learning difficulties that were said to be less severe. There is no other family history of autism. Methods/Case Report Chromosome analysis showed an abnormal karyotype identifying a duplication of the short arm of chromosome 3 from p13 to p14.3, 46,XY,dup(3)(p13p14.3). Additional microarray testing confirmed this duplication and defined the size as 14.9 Mb. Regions of homozygosity of 29.8 Mb were also identified, representing about 1% of the autosomal genome. The duplicated area includes over 70 genes, thirteen of which are known Mendelian disease genes (IL17RD, HESX1, APPL1, FLNB, DNASEIL3, PDHB, ACOX2, ATXN7, SLC25A26, EOGT, LMOD3, MITF, and FOXP1). Duplications of 3p are extremely rare and can be de novo or inherited from a parent with a balanced translocation. Individuals with these better-described chromosome 3p duplications typically present with intellectual and developmental disabilities, such as autism, as 3p duplications typically present with intellectual and developmental disabilities, such as autism and distinctive dysmorphic features. This duplication has never been reported as a known syndrome and has minimal overlap with copy number variants (CNVs) among healthy individuals. Results (if a Case Study enter NA) NA Conclusion Autism spectrum disorders are largely characterized by speech, communication, and social impairment of varying degrees. Diagnosis is typically made on clinical grounds, but in 14-35% of cases, a genetic basis for the disorder, typically either due to a single gene disorder or a chromosomal deletion/duplication, may be found. This case report describes a rare finding of a 14.9 Mb interstitial duplication on chromosome 3p.

Novel GRIA2 variant in a patient with atypical autism spectrum disorder and psychiatric symptoms: a case report

BackgroundAs sequencing technology has advanced in recent years, a series of synapse-related gene variants have been reported to be associated with autism spectrum disorders (ASDs). The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor is a subtype of the ionotropic glutamate receptor, whose number or composition changes can regulate the strength and plasticity of synapses.Case presentationHere, we report a de novo GRIA2 variant (NM_001083619.3: c.2308G > A, p.Ala770Thr) in a patient with obvious behavior regression and psychiatric symptoms. It encodes GluA2, which is the crucial subunit of the AMPA receptor, and the missense variation is predicted to result in instability of the protein structure.ConclusionsThe association between GRIA2 variants and onset of ASD symptoms is rare, and our study expands the spectrum of phenotypic variations. For patients with an unexplained etiology of ASD accompanied by psychiatric symptoms, genetic causes should be considered, and a complete genetic evaluation should be performed.

Comparison of serum thrombospondin-1 and thrombospondin-2 levels among children with autism spectrum disorder and healthy controls

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the etiology of which has not been clearly determined yet. There is increasing evidence that synaptic and dendritic changes are involved in the etiology of ASD. The aim of this study is to determine whether serum Thrombospondin-1 and Thrombospondin-2 differ between ASD patients and healthy controls. This study also investigates possible correlations between clinical symptomatology of ASD and serum Thrombospondin-1 and Thrombospondin-2 levels. Method: A total of 44 children with ASD and 21 healthy controls under 6 years of age were included in the study. Symptom severity and behavioral problems among children with ASD were evaluated by using Childhood Autism Rating Scale and Abnormal Behavior Checklist. Serum levels of Thrombospondin-1 and Thrombospondin-2 were measured by using commercial enzyme-linked immunosorbent assay kits. Result: No statistically significant differences were found between the two groups in terms of serum Thrombospondin-1 and Thrombospondin-2 levels. In addition, no correlation was determined between Thrombospondin-2 levels and clinical symptomatology and severity of ASD. However, the Thrombospondin-1 level was found to negatively correlated with the total score of Childhood Autism Rating Scale, inappropriate speech and stereotype subscale scores of Aberrant Behavior Checklist scale. Conclusion: Thrombospondin-1 might have a potential role in the etiopathogenesis of ASD. Further studies are required to clearly elucidate the association between Trombospondin-1 and ASD.

Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder

BackgroundContactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses. MethodA CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database. ResultsMost (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs. ConclusionsIntronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD.