JAMA. 2024 Apr 19. doi: 10.1001/jama.2024.5922. Online ahead of print.

NO ABSTRACT

PMID:38639978 | DOI:10.1001/jama.2024.5922

Neurol Sci. 2024 Apr 19. doi: 10.1007/s10072-024-07528-2. Online ahead of print.

ABSTRACT

BACKGROUND: Neurophysiological studies recognized that Autism Spectrum Disorder (ASD) is associated with altered patterns of over- and under-connectivity. However, little is known about network organization in children with ASD in the early phases of development and its correlation with the severity of core autistic features.

METHODS: The present study aimed at investigating the association between brain connectivity derived from MEG signals and severity of ASD traits measured with different diagnostic clinical scales, in a sample of 16 children with ASD aged 2 to 6 years.

RESULTS: A significant correlation emerged between connectivity strength in cortical brain areas implicated in several resting state networks (Default mode, Central executive, Salience, Visual and Sensorimotor) and the severity of communication anomalies, social interaction problems, social affect problems, and repetitive behaviors. Seed analysis revealed that this pattern of correlation was mainly caused by global rather than local effects.

CONCLUSIONS: The present evidence suggests that altered connectivity strength in several resting state networks is related to clinical features and may contribute to neurofunctional correlates of ASD. Future studies implementing the same method on a wider and stratified sample may further support functional connectivity as a possible biomarker of the condition.

PMID:38639894 | DOI:10.1007/s10072-024-07528-2

Hosp Pediatr. 2024 Apr 19:e2023007685. doi: 10.1542/hpeds.2023-007685. Online ahead of print.

NO ABSTRACT

PMID:38639041 | DOI:10.1542/hpeds.2023-007685

Front Psychiatry. 2024 Apr 4;15:1332441. doi: 10.3389/fpsyt.2024.1332441. eCollection 2024.

ABSTRACT

INTRODUCTION: The Pathway for Eating disorders and Autism developed from Clinical Experience (PEACE pathway) is a clinical pathway of adapted treatment for individuals with eating disorders and autism in the UK. This study aims to investigate multidisciplinary clinicians' views of the strengths and challenges of PEACE pathway adaptations, while identifying areas where further improvement is needed.

METHOD: Semi-structured interviews were conducted with 16 clinicians who worked on the PEACE pathway. Themes relevant to the benefits, challenges and areas of improvement were identified, and a thematic map was produced.

RESULTS: PEACE Pathway brought clinical benefits such as improved understanding of patients' perspective, improved flexibility and individualisation in clinicians' approach, increased patient engagement, and provision of resources that are helpful to all patients with or without autism. Benefits to the service included increase in autism awareness, clinicians' confidence, and team collaboration. Challenges were also identified, including difficulties in incorporating autism adaptations into existing treatment protocol, implementing PEACE at different levels of care, staff schedule conflicts, and increased pressure to meet patients' needs. Overall, there is a need for systemic improvement in aftercare and community support for autism, more suitable autism screening tool, and more structured guidelines for making adaptations.

CONCLUSIONS AND IMPLICATIONS: PEACE Pathway has brought clinical and service benefits, while also bringing practical challenges rooted in the difficulty in distinguishing between autism and eating disorder in comorbid population. Future areas of improvement are highlighted for PEACE resources as well as in the national support system for autistic individuals.

PMID:38638414 | PMC:PMC11024361 | DOI:10.3389/fpsyt.2024.1332441

Autism Dev Lang Impair. 2024 Apr 18;9:23969415241245096. doi: 10.1177/23969415241245096. eCollection 2024 Jan-Dec.

ABSTRACT

PURPOSE: Parent involvement is crucial for tailored early intervention programs. The Hanen More Than Words (HMTW) program is a parent-implemented language intervention for autistic children. The current study examined the effectiveness of the HMTW program delivered online among Chinese families.

METHODS: Using a randomized controlled trial design, 22 Chinese families of autistic children in Hong Kong completed the trial. Baseline and post-intervention assessments were conducted to measure changes in parent-child interaction, parents' use of linguistic facilitation techniques (LFTs), and children's communication skills. Additionally, the influence of parental self-efficacy and parenting stress on treatment outcomes was explored.

RESULTS: The intervention group demonstrated significant improvements in parent-child attention synchrony. Although the treatment effect on children's spontaneous communication was not significant, the intervention group showed a larger effect size compared to the controls. The treatment outcomes were mainly influenced by the parents' initial levels of self-efficacy but not by parenting stress.

CONCLUSION: These findings provide preliminary evidence of the effectiveness of the online-delivered HMTW program for Chinese parents of autistic children. Further research involving a larger sample and focusing on long-term effects is needed.

PMID:38638395 | PMC:PMC11025426 | DOI:10.1177/23969415241245096

Acta Neuropathol Commun. 2024 Apr 18;12(1):62. doi: 10.1186/s40478-024-01743-w.

ABSTRACT

BACKGROUND: Helsmoortel-Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal problems, visual impairments, and cardiac abnormalities. All patients exhibit heterozygous de novo nonsense or frameshift stop mutations in the Activity-Dependent Neuroprotective Protein (ADNP) gene, accounting for a prevalence of 0.2% of all autism cases worldwide. ADNP fulfills an essential chromatin remodeling function during brain development. In this study, we investigated the cerebellum of a died 6-year-old male patient with the c.1676dupA/p.His559Glnfs*3 ADNP mutation.

RESULTS: The clinical presentation of the patient was representative of the Helsmoortel-Van der Aa syndrome. During his lifespan, he underwent two liver transplantations after which the child died because of multiple organ failure. An autopsy was performed, and various tissue samples were taken for further analysis. We performed a molecular characterization of the cerebellum, a brain region involved in motor coordination, known for its highest ADNP expression and compared it to an age-matched control subject. Importantly, epigenome-wide analysis of the ADNP cerebellum identified CpG methylation differences and expression of multiple pathways causing neurodevelopmental delay. Interestingly, transcription factor motif enrichment analysis of differentially methylated genes showed that the ADNP binding motif was the most significantly enriched. RNA sequencing of the autopsy brain further identified downregulation of the WNT signaling pathway and autophagy defects as possible causes of neurodevelopmental delay. Ultimately, label-free quantification mass spectrometry identified differentially expressed proteins involved in mitochondrial stress and sirtuin signaling pathways amongst others. Protein-protein interaction analysis further revealed a network including chromatin remodelers (ADNP, SMARCC2, HDAC2 and YY1), autophagy-related proteins (LAMP1, BECN1 and LC3) as well as a key histone deacetylating enzyme SIRT1, involved in mitochondrial energy metabolism. The protein interaction of ADNP with SIRT1 was further biochemically validated through the microtubule-end binding proteins EB1/EB3 by direct co-immunoprecipitation in mouse cerebellum, suggesting important mito-epigenetic crosstalk between chromatin remodeling and mitochondrial energy metabolism linked to autophagy stress responses. This is further supported by mitochondrial activity assays and stainings in patient-derived fibroblasts which suggest mitochondrial dysfunctions in the ADNP deficient human brain.

CONCLUSION: This study forms the baseline clinical and molecular characterization of an ADNP autopsy cerebellum, providing novel insights in the disease mechanisms of the Helsmoortel-Van der Aa syndrome. By combining multi-omic and biochemical approaches, we identified a novel SIRT1-EB1/EB3-ADNP protein complex which may contribute to autophagic flux alterations and impaired mitochondrial metabolism in the Helsmoortel-Van der Aa syndrome and holds promise as a new therapeutic target.

PMID:38637827 | PMC:PMC11027339 | DOI:10.1186/s40478-024-01743-w

Res Dev Disabil. 2024 Apr 17;149:104729. doi: 10.1016/j.ridd.2024.104729. Online ahead of print.

ABSTRACT

BACKGROUND: Cultural-based literature focusing on Asian autistic immigrants living in Western countries is very limited.

AIMS: The present study is a quality improvement exercise aiming to fill the gap by investigating the employment needs of and barriers for Chinese autistic youth and young adults in Ontario, Canada.

METHODS & PROCEDURES: 71 individuals diagnosed with autism and 24 diagnosed with other mental illnesses, aged 12-29, participated in an online survey regarding their work readiness, work skills, interests, health and cultural concerns. Analyses were conducted to compare the autistic group and the mental health group.

OUTCOMES & RESULTS: Results show that the autistic sample has inferior (1) work habits related skills, (2) work style related skills, (3) level of independence, (4) skills to perform routine daily activities, (5) interpersonal skills at work, and (6) ability to tolerate visual and moving stimuli in the work environment. It is also found that the autistic group has more symptoms of depression, anxiety, and autism than that of the non-autistic group.

CONCLUSIONS & IMPLICATIONS: The study shed light into the unique needs and barriers of Chinese autistic young adults and the service gap in supporting their transition to employment.

PMID:38636251 | DOI:10.1016/j.ridd.2024.104729

Discov Ment Health. 2024 Apr 18;4(1):13. doi: 10.1007/s44192-024-00065-6.

ABSTRACT

Most autistic people experience difficulties in sensory processing, including interoceptive processing. For example, they often report subjective difficulties in the interoceptive processing of interoceptive input, such as difficulty in interpreting bodily signals, including hunger, thirst, and fatigue. However, whether these subjective interoceptive difficulties are from underlying problems in interoceptive accuracy remains unclear. This study investigated the relationship between subjective interoceptive difficulty and behavioral interoceptive accuracy in autistic adults and a control group. Subjective interoceptive accuracy was measured using an interoceptive sensitivity questionnaire, and behavioral interoceptive accuracy was measured using a heartbeat counting task. The results showed no significant relationship between subjective interoceptive difficulty and behavioral interoceptive accuracy in the autistic or control groups. This suggests that subjective interoceptive difficulty and behavioral interoceptive accuracy reflect different aspects of interoceptive processing. One possible interpretation is that autistic adults can identify individual local sensory inputs, such as heartbeats, however, they have difficulty integrating multiple inputs and recognizing internal body states such as hunger and fatigue.

PMID:38637435 | DOI:10.1007/s44192-024-00065-6

MMWR Morb Mortal Wkly Rep. 2024 Apr 18;73(15):358. doi: 10.15585/mmwr.mm7315a5.

NO ABSTRACT

PMID:38635498 | DOI:10.15585/mmwr.mm7315a5

Appl Neuropsychol Adult. 2024 Apr 18:1-8. doi: 10.1080/23279095.2024.2336201. Online ahead of print.

ABSTRACT

INTRODUCTION: Neuropsychological deficits in areas of Executive Functioning (EF), theory of mind, and central coherence have been well-documented among children and adolescents with autism spectrum disorder (ASD); however, there remains a significant gap in knowledge with regards to neuropsychological profile in adults with ASD. This study aims to investigate the intellectual functioning and neuropsychological profiles of a clinical population of adults with ASD.

METHODS: This cross-sectional study included 40 available autistic individuals referred to an adult developmental disorders clinic at a hospital between 2021 and 2022. All participants were assessed using the Stanford-Binet Intelligence Scale (SBIS), Autism Spectrum Quotient (AQ), Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R), and Social Responsiveness Scale (SRS).

RESULTS: Individuals with ASD exhibited lower IQ scores across all domains of the Stanford-Binet Intelligence Scale, compared to the general population, although the mean IQ scores remained within the normal range. Significant differences were observed in Full Scale IQ, Verbal IQ, Non-Verbal IQ, Fluid Reasoning, Knowledge, Quantitative Reasoning, Visual-Spatial Processing, and Working Memory compared to the general population. Additionally, autistic individuals' performance on verbal knowledge was higher compared to non-verbal knowledge. No significant correlations were found between the total and subscale scores of verbal and nonverbal IQ and AQ, RAADS-R, and SRS scores.

CONCLUSION: Considering the significant impacts of cognitive and executive function on the social and occupational aspects of autistic adults, further investigations in this area are warranted.

PMID:38635408 | DOI:10.1080/23279095.2024.2336201

J Autism Dev Disord. 2024 Apr 18. doi: 10.1007/s10803-024-06306-5. Online ahead of print.

ABSTRACT

This study applied the functional near-infrared spectroscopy (fNIRS) to investigate frontal activity in autism when performing verbal fluency test and emotion recall task. We recruited 32 autistic adults without intellectual disability and 30 typically-developing controls (TDC). Prefrontal hemodynamic changes were evaluated by fNIRS when the participants performed the verbal fluency test and emotion recall task. fNIRS signals in the prefrontal cortex were compared between autism and TDC. Compared to TDC, autistic adults showed comparable performance on the verbal fluency test but exhibited lower frontal activity on the vegetable category. In the verbal fluency test, left frontal activity in TDC significantly increased in the vegetable category (vs. fruit category). In the emotion recall task, left frontal activity increased significantly in TDC when recalling emotional (vs. neutral) events. This increase of left frontal activity on the more difficult works was not found in autism. Similarly, brain activities were related to test performance only in TDC but not in autism. In addition, more severe social deficits were associated with lower frontal activity when recalling emotional events, independent of autism diagnosis. Findings suggested reduced frontal activity in autism, as compared to TDC, when performing verbal fluency tests. The reduction of left frontal activation in verbal fluency test and emotion recall tasks might reflect on the social deficits of the individual. The fNIRS may potentially be applied in assessing frontal lobe function in autism and social deficits in general population. Trial registration number: NCT04010409.

PMID:38635133 | DOI:10.1007/s10803-024-06306-5

J Autism Dev Disord. 2024 Apr 18. doi: 10.1007/s10803-024-06303-8. Online ahead of print.

ABSTRACT

Children with autism spectrum disorder (ASD) are five times more likely to have feeding difficulties than neurotypical peers, although the majority of evidence describes feeding difficulty in children age 2 years and older. The purpose of this study is to systematically review the literature on feeding characteristics of children age 0-24 months who were later diagnosed with ASD with an emphasis on the measurement tools used to assess these feeding behaviors. We conducted a systematic review of the literature using PRISMA guidelines. Using selected keywords, a search was conducted using PubMed, PsycINFO, and CINAHL databases for relevant articles to identify feeding characteristics in infants and toddlers (age 0-24 months) later diagnosed with ASD. Sixteen studies were selected for this review by two independent reviewers. Among the selected studies, feeding difficulties were reported in all infant oral feeding modalities (breastfeeding, bottle feeding, and complementary feeding) by infants later diagnosed with ASD. However, the evidence was conflicting among studies regarding feeding characteristics, such as sucking differences while breastfeeding, use of the spoon with feedings, and preference of solid food texture, that presented in infants later diagnosed with ASD. A lack of consistent measurement of feeding behaviors in infants later diagnosed with ASD contributes to the difficulty in comparison across studies. Future research should focus on developing targeted, validated instruments for measuring feeding difficulty in this population with emphasis on breastfeeding and bottle feeding difficulty.

PMID:38635132 | DOI:10.1007/s10803-024-06303-8

J Autism Dev Disord. 2024 Apr 18. doi: 10.1007/s10803-024-06348-9. Online ahead of print.

ABSTRACT

The post-secondary transition for autistic youth is a complex process, with hopes and expectations serving as malleable mediators often overlooked in research and practice. Career awareness, exploration, and counseling services play a critical role in facilitating vocational transition, but the vocational hopes and expectations of autistic youth and their parents are often disregarded. This study aims to explore these aspirations and their impact on the vocational transition process, seeking to harmonize elements to better align with the needs of autistic youth and their families. This study used a focus group design involving group interviews with three participant groups: autistic transition-aged youth, parents, and practitioners. The findings reveal five key themes: 1) Accepting Disability or Constrained by Ableism: Resisting Marginalization, 2) Finding the Sweet Spot: Are Parents and Youth's Expectations Too High or Too Low, 3) Market Forces at Work-Finding a Meaningful Vocational Path in a Capitalist Society, 4) Despite Meticulous Planning, there is a Disconnect Between Needs and Resources, and 5) The Hills and Valleys of Finding Resilience. Navigating the multifaceted landscape of vocational transition planning for autistic youth necessitates a collaborative and flexible approach. Identified tensions serve as opportunities for growth and transformation. Recognizing and addressing system shortcomings is crucial for informed decision-making. Challenges extend beyond individual circumstances, reflecting broader systemic issues, and identifying these gaps allows for a comprehensive understanding of available resources, cultivating a basis of hope as uncertainties are addressed.

PMID:38635131 | DOI:10.1007/s10803-024-06348-9

J Autism Dev Disord. 2024 Apr 18. doi: 10.1007/s10803-024-06352-z. Online ahead of print.

ABSTRACT

Individuals with Autism Spectrum Disorder (ASD) present atypical sensory processing in the perception of moving stimuli and biological motion. The present study aims to explore the performance of young adults with ASD in a time to contact (TTC) estimation task involving social and non-social stimuli. TTC estimation involves extrapolating the trajectory of a moving target concealed by an occluder, based on the visible portion of its path, to predict the target's arrival time at a specific position. Sixteen participants with a diagnosis of level-1 ASD (M = 19.2 years, SE = 0.54 years; 3 F, 13 M) and sixteen participants with TD (M = 22.3 years, SE = 0.44 years; 3 F, 13 M) took part in the study and underwent a TTC estimation task. The task presented two object types (a car and a point-light walker), different object speeds, occluder lengths, motion directions and motion congruency. For the car object, a larger overestimation of TTC emerged for ASDs than for TDs, whereas no difference between ASDs and TDs emerged for the point-light walker. ASDs exhibited a larger TTC overestimation for the car object than for the point-light walker, whereas no difference between object types emerged for TDs. Our results indicated an atypical TTC estimation process in young adults with ASD. Given its importance in daily life, future studies should further explore this skill. Significant effects that emerged from the analysis are discussed.

PMID:38635130 | DOI:10.1007/s10803-024-06352-z

Autism Res. 2024 Apr 18. doi: 10.1002/aur.3135. Online ahead of print.

ABSTRACT

It is crucial to arrive at a comprehensive understanding of the types of daily activities autistic adults typically engage in. However, previous research has almost exclusively focused on vocational or education activities. Further, it remains unclear how and whether specific daily activities participation rates change proportionally over time, vary by gender, or compare to nationally representative data. Utilizing eight annual data waves from the Netherlands Autism Register (NAR) this study aims to bridge this gap. Participants were 2449 autistic adults who indicated their participation in 18 daily activities. Results suggest that autistic adults engaged most frequently in vocational activities (e.g., paid employment, study) and participation rates were stable over time. Participation rates in non-vocational activities (e.g., hobbies, homemaking) fluctuated proportionally over time, with reports of no structured daytime activities reducing over time. Labor force participation amongst NAR participants was significantly lower than Dutch population data for the same time periods. Unemployment rates fluctuated, and were significantly higher than population data, but not for all time points. Females compared to males were overrepresented in unpaid daily activities (e.g., study, volunteer, housemaker) and work incapacitation, and underrepresented in paid employment. Employment differences in gender corresponded to national data. These findings characterize more clearly the daily activities of autistic adults, and highlights areas where support may have greater impact (e.g., females in employment).

PMID:38634518 | DOI:10.1002/aur.3135

Autism. 2024 Apr 18:13623613241245749. doi: 10.1177/13623613241245749. Online ahead of print.

ABSTRACT

This study aimed to explore the impact of Autistic identity (i.e. feeling like you belong to the Autistic community), sensory profiles (e.g. being over or under responsive to sensations) and camouflaging behaviours (i.e. masking) on eating disorder symptoms in Autistic adults. 180 Autistic people were recruited from the community and NHS. The Autistic people completed online questionnaires measuring Autistic identity, sensory profiles, camouflaging behaviours, autistic traits and eating disorder symptoms. The analysis showed that higher levels of camouflaging behaviour predicted higher levels of eating disorder symptoms. Sensory profiles were related to but did not predict eating disorder symptoms and there was no relationship between level of Autistic identity and eating disorder symptoms. This shows that camouflaging is the most important predictor of eating disorder symptoms in Autistic people, and warrants further exploration.

PMID:38634458 | DOI:10.1177/13623613241245749

Front Public Health. 2024 Apr 3;12:1365877. doi: 10.3389/fpubh.2024.1365877. eCollection 2024.

ABSTRACT

Health insurance stands as a pivotal facet of social wellbeing, with profound implications for the overarching landscape of economic development. The existing research, however, lacks consensus on the relationship between health insurance and economic performance and provides no evidence about the magnitude of the correlation. This lack of information seriously impedes the high-quality development of the healthcare system. Therefore, to scientifically elucidate the relationship between the two, this study involved a meta-analysis, analyzing 479 effect values derived from 34 independent research samples. The results reveal a strongly positive correlation between health insurance and economic performance [r = 0.429, 95% CI = (0.381, 0.475)]. Findings show that health insurance in developed countries more effectively fosters economic performance than in developing countries. Moreover, public health insurance exerts a stronger promoting effect on economic performance than commercial health insurance. The relationship between health insurance and economic performance is moderated by data type, research method, country of sample origin, literature type, journal impact factor, publication year, type of health insurance, and the research populations. Based on meta-analysis, this study not only scientifically responds to the controversy of the relationship between health insurance and economic performance, and the magnitude of a correlation, but also further reveals the inner conduction mechanism between the two. Our research findings are meaningful for policymakers to choose an appropriate healthcare strategy according to their unique attributes, propelling sustainable economic development.

PMID:38633240 | PMC:PMC11021690 | DOI:10.3389/fpubh.2024.1365877

medRxiv [Preprint]. 2024 Apr 4:2024.04.03.24305278. doi: 10.1101/2024.04.03.24305278.

ABSTRACT

Autism Spectrum Disorder (ASD) arises from complex genetic and environmental factors, with inherited genetic variation playing a substantial role. This study introduces a novel approach to uncover moderate effect size (MES) genes in ASD, which individually do not meet the ASD liability threshold but collectively contribute when paired with specific other MES genes. Analyzing 10,795 families from the SPARK dataset, we identified 97 MES genes forming 50 significant gene pairs, demonstrating a substantial association with ASD when considered in tandem, but not individually. Our method leverages familial inheritance patterns and statistical analyses, refined by comparisons against control cohorts, to elucidate these gene pairs' contribution to ASD liability. Furthermore, expression profile analyses of these genes in brain tissues underscore their relevance to ASD pathology. This study underscores the complexity of ASD's genetic landscape, suggesting that gene combinations, beyond high impact single-gene mutations, significantly contribute to the disorder's etiology and heterogeneity. Our findings pave the way for new avenues in understanding ASD's genetic underpinnings and developing targeted therapeutic strategies.

PMID:38633780 | PMC:PMC11023658 | DOI:10.1101/2024.04.03.24305278

Disabil Rehabil. 2024 Apr 18:1-7. doi: 10.1080/09638288.2024.2340123. Online ahead of print.

ABSTRACT

PURPOSE: To compare (1) motor proficiency of persons diagnosed in adulthood with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) with normative values of motor proficiency, and (2) motor proficiency between persons with ADHD and those with ASD diagnosed in adulthood.

METHODS: A total of 153 adults (median age 32 years, 36% women) participated in this cross-sectional study. Fifty-three persons with predominately inattentive presentation (ADHD-I), 67 persons with combined presentation (ADHD-C), and 33 persons with ASD performed the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2). One-sample binominal tests were used to compare motor proficiency against standardized norms of BOT-2 for young adults. One-way ANOVAs and Kruskal-Wallis tests were used to compare test outcomes between the groups.

RESULTS: The total sample showed significantly impaired motor proficiency in comparison to norms in all test domains (p < 0.001-0.006), except for fine motor skills. The ASD group showed significantly poorer body coordination compared with the ADHD-I and ADHD-C groups, with a moderate effect size (p = 0.003-0.02, η2 = 0.061).

CONCLUSIONS: Motor proficiency is impaired in most persons with ADHD or ASD diagnosed in adulthood, suggesting that motor assessment should be included in clinical examinations of adults with suspected neurodevelopment disorders.

PMID:38632964 | DOI:10.1080/09638288.2024.2340123

J Neurodev Disord. 2024 Apr 17;16(1):17. doi: 10.1186/s11689-024-09530-3.

ABSTRACT

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource's (ClinGen's) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen's BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders.

PMID:38632549 | DOI:10.1186/s11689-024-09530-3