Cause Of Autism Research Articles

Heritability of Sound Processing Deficits in Autism: Neural Insights

Heritability of Sound Processing Deficits in Autism: Neural Insights

Screening for Fragile X Syndrome Among Filipino Children with Autism Spectrum Disorder.

Individuals with autism spectrum disorder present with difficulties in social communication, restricted interests or behaviors and other co-morbidities. About 2 to 10% of cases of autism have a genetic cause, and Fragile X Syndrome (FXS) is reported in 0 to 6.5% of individuals with autism. However, the FXS and premutation prevalence among Filipino children has never been reported. The aim of the study was to establish the presence of FXS or premutation carriers among Filipino children with autism and to describe the phenotypic characteristic of cases identified. Blood was collected from 235 children aged 2-6 years old and diagnosed with autism. Samples were analyzed using PCR methods to amplify CGG repeats in the FMRI gene. The diagnosis of autism was confirmed through the Autism Diagnostic Observation Schedule-2. Additional characteristics were documented from a physical examination, Griffiths Scales of Child Development assessment and a parent-answered questionnaire using the Vineland Adaptive Behavior Scale. Fragile X testing through PCR methods in 235 children with diagnosed autism showed 220 (93.6%) were negative, no full mutations, 1 (0.436%) premutation carrier and 14 (5.95%) cases contained intermediate alleles. The FXS testing was limited to confirmed cases of autism, which is considered a high-risk group and does not provide prevalence for the general Filipino population. Subjects were self-referred or referred by clinicians, which may not represent the Filipino autism population with a bias towards those with means for clinical consultations and ability to travel to the place of testing. Samples were not measured for mosaicism, DNA methylation or AGG interspersion patterns. These may have effects on the CGG repeat expansion and overall presentation of FXS. Findings from a single premutation carrier cannot characterize features distinctly present in Filipinos with the mutation. Nevertheless, these results support the data that the prevalence of FXS in Asian populations may be lower than non-Asian populations. This can contribute to a better understanding of FXS and genetic causes of autism in the Philippines and other Asian populations.

Does Vaccination Increase the Risk of Autism Spectrum Disorder?

Autism spectrum disorder (ASD) is a developmental disorder that can cause significant social, communicative, and behavioral difficulties. With autism rates rising dramatically in recent years, researchers and concerned parents have theorized the causes of autism, and the subject has received much attention. Is the high rate of autism now due to increased diagnosis and reporting, changing autism definitions, or a rise in the number of people with ASD? People started to blame vaccines as a cause of the increased number of people with ASD. Vaccines and their connection to autism have been the subject of continuous debate. Some parents are concerned that vaccines, particularly the measles-mumps-rubella (MMR) vaccine and preservatives used in other childhood vaccines, may play a role in developing autism in their children. This systemic review explores the link between vaccination and autism in children. We conducted a literature search using PubMed and Google Scholar. We included papers written in the English language from 1998 to 2022, conducting human research that examines the relationship between vaccination and the development of autism using appropriate quality assessment tools. Two reviewers independently reviewed the content of the included studies. In total, 21 studies were deemed eligible.

Misinformation About COVID-19 Vaccines on Social Media: Rapid Review.

BackgroundThe development of COVID-19 vaccines has been crucial in fighting the pandemic. However, misinformation about the COVID-19 pandemic and vaccines is spread on social media platforms at a rate that has made the World Health Organization coin the phrase infodemic. False claims about adverse vaccine side effects, such as vaccines being the cause of autism, were already considered a threat to global health before the outbreak of COVID-19.ObjectiveWe aimed to synthesize the existing research on misinformation about COVID-19 vaccines spread on social media platforms and its effects. The secondary aim was to gain insight and gather knowledge about whether misinformation about autism and COVID-19 vaccines is being spread on social media platforms.MethodsWe performed a literature search on September 9, 2021, and searched PubMed, PsycINFO, ERIC, EMBASE, Cochrane Library, and the Cochrane COVID-19 Study Register. We included publications in peer-reviewed journals that fulfilled the following criteria: original empirical studies, studies that assessed social media and misinformation, and studies about COVID-19 vaccines. Thematic analysis was used to identify the patterns (themes) of misinformation. Narrative qualitative synthesis was undertaken with the guidance of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 Statement and the Synthesis Without Meta-analysis reporting guideline. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tool. Ratings of the certainty of evidence were based on recommendations from the Grading of Recommendations Assessment, Development and Evaluation Working Group.ResultsThe search yielded 757 records, with 45 articles selected for this review. We identified 3 main themes of misinformation: medical misinformation, vaccine development, and conspiracies. Twitter was the most studied social media platform, followed by Facebook, YouTube, and Instagram. A vast majority of studies were from industrialized Western countries. We identified 19 studies in which the effect of social media misinformation on vaccine hesitancy was measured or discussed. These studies implied that the misinformation spread on social media had a negative effect on vaccine hesitancy and uptake. Only 1 study contained misinformation about autism as a side effect of COVID-19 vaccines.ConclusionsTo prevent these misconceptions from taking hold, health authorities should openly address and discuss these false claims with both cultural and religious awareness in mind. Our review showed that there is a need to examine the effect of social media misinformation on vaccine hesitancy with a more robust experimental design. Furthermore, this review also demonstrated that more studies are needed from the Global South and on social media platforms other than the major platforms such as Twitter and Facebook.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42021277524; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021277524International Registered Report Identifier (IRRID)RR2-10.31219/osf.io/tyevj

Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this form of syndromic autism.SIGNIFICANCE STATEMENT Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in primary visual cortex of the animal model for MECP2-duplication syndrome, a high-penetrance single-gene cause of autism. Visual-evoked activity was abnormally decoupled from endogenous activity in mutant mice, suggesting in line with the influential "hypo-priors" theory of autism that sensory priors embedded in endogenous activity may have less influence on perception in autism.

RWD48 Inpatient Resource Utilization Outcomes Among Patients Living with Fragile X Syndrome and Comorbid Autism Spectrum Disorder in the US

Fragile X Syndrome (FXS) is the most common heritable cause of autism and intellectual disability. Autism Spectrum Disorder (ASD) is characterized by social interaction and communication impairment. Individuals with FXS and ASD have greater prevalence of seizures, persistence of sleep problems, and increased behavior problems.

Perception, Beliefs, and Causal Attribution of Autism Early Signs in Ecuadorian General Population.

The identification and diagnosis of children with autism currently rely on behavioral presentation and developmental history. Cultural norms and other socio-demographic factors can influence what is expected or non-expected behaviors in a developing child. Perceptions, beliefs, and causal attribution of early signs can influence families’ help-search behaviors. Lack of recognition of autism’s first manifestations can critically delay the age of diagnosis, the provision of informed guidance to families, and the implementation of adapted interventions during the critical period of early development. Furthermore, a lack of understanding of early signs as the manifestations of a developmental condition may increase stigma and non-conventional explanations. Still, cultural and socio-demographic factors are largely understudied, particularly in low-and middle-income settings. Based on the hypothesis that non-specialists such as family members and friends are one of the first sources of referral in Latin American contexts, we aimed to study the general population’s perceptions and the explanatory causes of autism’s early signs. One-hundred-and-eighty-three Ecuadorian adults responded to a questionnaire developed for this study, describing sixteen ASD-related behaviors. Results indicated that, with the exemption of language impairment and self-injurious behaviors, a substantial proportion of participants did not endorse many behaviors as “concerning and requiring professional attention.” Also, language impairment was the only behavior identified as related to a developmental disorder. Additionally, most participants attributed the majority of behaviors listed in the questionnaire to causes unrelated to ASD, such as child personality. We discuss the impact of those findings in clinical practice and on awareness programs.

Dog Therapy in Supporting the Rehabilitation Process of Children with Autism

Introduction: Autism is not a specific condition. It is, however, a comprehensive disorder of psychomotor and social development. A number of factors, both environmental (family-related) and genetic, are believed to be the cause of autism. The percentage of children affected by autism has been increasing over the past 20 years. It is assumed that statistically, approximately 20 children in every 10,000 will become affected by this condition. Autism is 4 times more common in boys than in girls. The disorder is characterised by impaired mental growth, and, consequently, social and motor development. Research objective: The aim of the article is to present the role of dog therapy in supporting the process of therapeutic rehabilitation among children with autism. In particular, the following aspects were taken into account: breeds of canines used in dog therapy, mechanisms of influence concerning dog therapy on the child's body, as well as the forms and results obtained. Material and methods: The work is a narrative review. It was written on the basis of the document analysis method with the use of quantitative and qualitative techniques, as well as database searches for Polish and foreign scientific literature on the subject, i.e. Web of Science, PubMed and Google Scholar. In the article, the research results are presented in relation to the efficiency of applying dog therapy in the treatment of autistic children between 2002 and 2017, with emphasis on foreign literature. Results: The most commonly used forms of dog therapy used are: Animal Assisted Activity (AAA), Animal Assisted Therapy (AAT) and Animal Assisted Education (AAE). Conclusions: The use of dogs in the process of therapeutic rehabilitation has positive influence both on the autistic child and his/her family environment. It helps cope better with many difficulties and motivates to take up more activities. Dog therapy affects all spheres of personal development, i.e. mental, motor and socio-emotional.

Research of the Problem of Autism and Autistic Disorders: Theoretical Aspect

The causes of autism remain insufficiently differentiated. It is unlikely that any single disorder can be considered as the only cause of various symptoms and severity of autistic disorders. Although the specific causes of autism remain unclear, significant progress has been made in understanding the possible mechanisms of the disease. Turning to historical sources, we find that the origin and origin of the term "autism" are associated with forming a system of knowledge on the problem of diagnosis and further therapeutic work with children who need unique approaches to learn and educate. Analysis of the classifications of autism reveals the ambiguity of approaches to them. The first attempts at differentiation in the middle of childhood autism syndrome were clinical classifications based on the syndrome's etiology. They play a significant role in developing adequate approaches to providing medical care to children with autism. Psychological and pedagogical tasks required other approaches to determine, depending on the specific situation, the specialization, strategy, and tactics of correctional work. First of all, there was a search for prognostic signs that would assess the possibilities of mental and social development of children in this category. To this end, some scholars have put forward criteria for assessing speech and intellectual development. The analysis of difficulties of the unanimous possibility of classification on separate indicators of mental development of the child (intelligence, speech, behavior, self-regulation, etc.) can be explained by parallel existence of classifications operating today in world practice.

Human Fetal Brain Magnetic Resonance Imaging (MRI) Tells Future Emergence of Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which can result from a range of observed symptoms pertaining to social, emotional, and cognitive processing difficulties especially regarding communication of their own feelings, opinions, and thoughts with others. Although a diagnosis received by 1 in 68 children in the United States, a cause for autism is still unknown. Both genetic and environmental factors during prenatal and postnatal development are believed to account for the emergence of ASD. It is known that early treatment improves language and cognitive abilities later. However, currently, the earliest diagnosis of ASD can be made only around 18 months of age. It is critical to be aware of an altered initial brain anatomy in ASD for better predicting what aspects of brain function will likely preferentially and precociously deteriorate, which would allow for potentially earlier/better prevention and treatment. We hypothesized that prospective ASD patients will show region‐specific abnormalities in developmental stages. We have used retrospective clinical brain MRI of the fetuses who were diagnosed as ASD in later age to obtain earliest MRI‐based regional volumetric biomarkers. Thirty‐nine fetuses (mean age 24.87 ± 5.05 gestational week [GW]) were included in this study (9 prospective ASD patients, 20 neurotypical controls, 6 non‐ASD controls with neurological comorbidities observed in the prospective ASD patients, and 4 non‐ASD controls with non‐neurological comorbidities observed in the prospective ASD patients. After preprocessing, the images were segmented automatically with an atlas‐based automated anatomical labeling method. A set of three‐factor ANOVA was performed for lobar and regional comparisons of the segmented brain regions. The insula/insular lobe showed statistically significantly larger volume in ASD than that in all three control groups in the lobar comparison. In the regional comparison, the ASD group had statistically significantly larger amygdala, hippocampal commissure, and insula compared to the non‐ASD controls with neurological and non‐neurological comorbidities. Our results suggest that an increased volume of the insula/insular lobe may be a strong prenatal MRI biomarker that could predict the emergence of ASD later in life. The larger amygdala and hippocampal commissure could be additional biomarkers for identifying such prospective ASD patients.

Community Knowledge about Autism Spectrum Disorder in the Kingdom of Saudi Arabia

Objectives: To explore the knowledge of the general community in Saudi Arabia about autism spectrum disorder. Method: A cross-sectional study was conducted for the period between June and September 2021 in Saudi Arabia using an online questionnaire tool. The questionnaire tool was developed based on a literature review. The questionnaire tool consists of 34 items that assess knowledge about autism spectrum disorder in terms of its etiology, autistic patient features, autistic children’s abilities and needs, and autistic adults’ abilities and needs. The total score for each subscale was used to define the level of knowledge of it. Correct answers were given a score of one, and the total score for each subscale was used to describe the level of knowledge of it. Logistic regression was used to identify predictors of good knowledge about autism spectrum disorder (defined as a total score equal or above the mean score of the study participants). Results: This study enlisted the participation of 500 people. The participants’ overall understanding of autism spectrum disorder was moderate, with a mean score of 20.6 (SD: 5.6) out of 34, or 60.6%. The participants’ knowledge levels ranged from 32.2% to 77.5%. The items about the abilities and needs of adolescents and young people with autism had the highest degree of knowledge (77.5%). The items about autism’s causes had the lowest level of expertise (32.2%). When compared to others, females, those with a master’s degree, and those working in the healthcare field had a higher likelihood of knowing more about the autism spectrum condition. (p ≤ 0.05). Conclusion: Knowledge about autism spectrum disorder in Saudi Arabia is moderate. Social media channels and healthcare centers should be used to conduct educational campaigns for parents. The goal of this educational campaign should be to improve parents’ ability to recognize the causes of autism.

Molecular screening for fragile X syndrome in children with unexplained intellectual disability and/or autistic behaviour

Fragile X syndrome (FXS, OMIM #300624) is the most common inherited form of intellectual disability and the leading monogenic cause of autism.

Exome Evaluation of Autism-Associated Genes in Amazon American Populations.

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group.

Is Genetics Implicated in the Causation of Autism?

Is Genetics Implicated in the Causation of Autism?

Behavior Problems and Social Competence in Fragile X Syndrome: A Systematic Review.

Fragile X syndrome (FXS) causes intellectual disability and is the known leading cause of autism. Common problems in FXS include behavior and social problems. Along with syndromic characteristics and autism comorbidity, environmental factors might influence these difficulties. This systematic review focuses on the last 20 years of studies concerning behavior and social problems in FXS, considering environmental and personal variables that might influence both problems. Three databases were reviewed, leading to fifty-one studies meeting the inclusion criteria. Attention deficit hyperactivity disorder (ADHD) problems remain the greatest behavior problems, with behavioral problems and social competence being stable during the 20 years. Some developmental trajectories might have changed due to higher methodological control, such as aggressive behavior and attention problems. The socialization trajectory from childhood to adolescence remains unclear. Comorbidity with autism in individuals with FXS increased behavior problems and worsened social competence profiles. At the same time, comparisons between individuals with comorbid FXS and autism and individuals with autism might help define the comorbid phenotype. Environmental factors and parental characteristics influenced behavior problems and social competence. Higher methodological control is needed in studies including autism symptomatology and parental characteristics. More studies comparing autism in FXS with idiopathic autism are needed to discern differences between conditions.

LRFN5 locus structure is associated with autism and influenced by the sex of the individual and locus conversions.

LRFN5 is a regulator of synaptic development and the only gene in a 5.4 Mb mammalian‐specific conserved topologically associating domain (TAD); the LRFN5 locus. An association between locus structural changes and developmental delay (DD) and/or autism was suggested by several cases in DECIPHER and own records. More significantly, we found that maternal inheritance of a specific LRFN5 locus haplotype segregated with an identical type of autism in distantly related males. This autism‐susceptibility haplotype had a specific TAD pattern. We also found a male/female quantitative difference in the amount histone‐3‐lysine‐9‐associated chromatin around the LRFN5 gene itself (p < 0.01), possibly related to the male‐restricted autism susceptibility. To better understand locus behavior, the prevalence of a 60 kb deletion polymorphism was investigated. Surprisingly, in three cohorts of individuals with DD (n = 8757), the number of deletion heterozygotes was 20%–26% lower than expected from Hardy–Weinberg equilibrium. This suggests allelic interaction, also because the conversions from heterozygosity to wild‐type or deletion homozygosity were of equal magnitudes. Remarkably, in a control group of medical students (n = 1416), such conversions were three times more common (p = 0.00001), suggesting a regulatory role of this allelic interaction. Taken together, LRFN5 regulation appears unusually complex, and LRFN5 dysregulation could be an epigenetic cause of autism.Lay SummaryLRFN5 is involved with communication between brain cells. The gene sits alone in a huge genomic niche, called the LRFN5 locus, of complex structure and high mammalian conservation. We have found that a specific locus structure increases autism susceptibility in males, but we do not yet know how common this epigenetic cause of autism is. It is, however, a cause that potentially could explain why higher‐functioning autism is more common in males than females.

Hyperexcitability and Homeostasis in Fragile X Syndrome.

Fragile X Syndrome (FXS) is a leading inherited cause of autism and intellectual disability, resulting from a mutation in the FMR1 gene and subsequent loss of its protein product FMRP. Despite this simple genetic origin, FXS is a phenotypically complex disorder with a range of physical and neurocognitive disruptions. While numerous molecular and cellular pathways are affected by FMRP loss, there is growing evidence that circuit hyperexcitability may be a common convergence point that can account for many of the wide-ranging phenotypes seen in FXS. The mechanisms for hyperexcitability in FXS include alterations to excitatory synaptic function and connectivity, reduced inhibitory neuron activity, as well as changes to ion channel expression and conductance. However, understanding the impact of FMR1 mutation on circuit function is complicated by the inherent plasticity in neural circuits, which display an array of homeostatic mechanisms to maintain activity near set levels. FMRP is also an important regulator of activity-dependent plasticity in the brain, meaning that dysregulated plasticity can be both a cause and consequence of hyperexcitable networks in FXS. This makes it difficult to separate the direct effects of FMR1 mutation from the myriad and pleiotropic compensatory changes associated with it, both of which are likely to contribute to FXS pathophysiology. Here we will: (1) review evidence for hyperexcitability and homeostatic plasticity phenotypes in FXS models, focusing on similarities/differences across brain regions, cell-types, and developmental time points; (2) examine how excitability and plasticity disruptions interact with each other to ultimately contribute to circuit dysfunction in FXS; and (3) discuss how these synaptic and circuit deficits contribute to disease-relevant behavioral phenotypes like epilepsy and sensory hypersensitivity. Through this discussion of where the current field stands, we aim to introduce perspectives moving forward in FXS research.

Mutations in the COL18A1 gen associated with knobloch syndrome and structural brain anomalies: a novel case report and literature review of neuroimaging findings

ABSTRACT . COL18A1 gene mutations have been associated with Knobloch syndrome, which is characterized by ocular and brain abnormalities. Here we report a 4.5 years-old male child with autism and two novel COL18A1 mutations (NM_030582.4: c.1883_1891dup and c.1787C>T). Hypermetropic astigmatism, but not brain migration disorders, was observed. However, an asymmetric pattern of cerebellar perfusion and a smaller arcuate fascicle were found. Low levels of collagen XVIII were also observed in the patient´s serum. Thus, biallelic loss-of-function mutations in COL18A1 may be a new cause of autism without the brain malformations typically reported in patients with Knobloch syndrome.

A Study to Assess the Effectiveness of Structured Teaching Programme on Knowledge and Attitude Regarding Childhood Behaviour Disorder Autism Among Mothers of Selected Developmental Centres of Agartala, Tripura, India

Background of the study: Autism is a Global burden including in our country India. Autism in the developmentaldisorder included under the umbrella of the pervasive development disorder. Childhood developmental disorderAutism characterized by deficits in social interaction, communication with unusual repetitive behaviour. Usuallythey live in their won world. Event they may show no interest what is happening around their. They remain usuallyin their won world. Socialization, education are big challenge for mothers whose has the child with Autism. Becausein the way of development of such children needed specialised knowledge and attitude of mothers includingcaregivers, parents and teachers. Keeping mind the concurrent, the present study aims to progression of awarenessand development of childhood behaviour disorder Autism in Tripura, Agartala as well as in our country India.Materials and methods: Present study is a quasi-experimental research design.500 mothers of Vidya WelfareSociety and Tripura Medical College &amp; Dr.B.R.A.M Teaching Hospital, Agartala with child with Autismwere selected by purposive sampling technique. Dr. Nola Pender theory was implied in this study. 40 Semistructured questionnaire of knowledge and 12 Attitude were administered after structured teaching programme.The estimated reliability of the tool is 0.90. Data were analysed by inferential quantitative method.Results: The results of post-test knowledge showed the increase in knowledge regarding childhood behaviourdisorder autism. The reliability of the tool structure knowledge questionnaire was 0.82 and the tool forattitude was 0.90. The enhancement of knowledge regarding meaning and characteristics of autism was 38.7%,enhancement of knowledge regarding causes of autism was 41.2% and enhancement of knowledge regardingmanagement was 39.6% and the over all aspects of knowledge was 39.4%. The increase or enhancement ofattitude regarding childhood behavioural disorder autism was 19.1%. The paired t-test was carried out and itwas found to be remain significant for knowledge and attitude at p&lt;0.001 level. Results implied that increase inknowledge and the increase in attitude regarding childhood behavioural disorder autism among mothers childwith autism in this present study.Conclusion: Mothers with more education and financial empowerment will make easier path to managechildhood behaviour disorder Autism. This study also suggest for more family support, Intra-natal care ,toprovide child joint family environment, access of others institutional health care and counselling centres facilityfor behaviour disorder autism of child also need for proper knowledge and attitude of mothers’ child with autism.

High Throughput Small Molecule Screen for Reactivation of FMR1 in Fragile X Syndrome Human Neural Cells.

Fragile X syndrome (FXS) is the most common inherited cause of autism and intellectual disability. The majority of FXS cases are caused by transcriptional repression of the FMR1 gene due to epigenetic changes that are not recapitulated in current animal disease models. FXS patient induced pluripotent stem cell (iPSC)-derived gene edited reporter cell lines enable novel strategies to discover reactivators of FMR1 expression in human cells on a much larger scale than previously possible. Here, we describe the workflow using FXS iPSC-derived neural cell lines to conduct a massive, unbiased screen for small molecule activators of the FMR1 gene. The proof-of-principle methodology demonstrates the utility of human stem-cell-based methodology for the untargeted discovery of reactivators of the human FMR1 gene that can be applied to other diseases.