Frequency and Complexity of De Novo Structural Mutation in Autism.

Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.

Community-Academic Partnerships: A Systematic Review of the State of the Literature and Recommendations for Future Research.

POLICY POINTS: Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research, to provide firsthand knowledge and insight. Based on our systematic review of major literature databases, we recommend using a single term, community-academic partnership (CAP), and a conceptual definition to unite multiple research disciplines and strengthen the field. Interpersonal and operational factors that facilitate or hinder the collaborative process have been consistently identified, including "trust among partners" and "respect among partners" (facilitating interpersonal factors) and "excessive time commitment" (hindering operational factor). Once CAP processes and characteristics are better understood, the effectiveness of collaborative partner involvement can be tested. CONTEXT: Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research. Community stakeholders can provide firsthand knowledge and insight, thereby increasing research relevance and feasibility. Despite the greater emphasis and use of community-academic partnerships (CAP) across multiple disciplines, definitions of partnerships and methodologies vary greatly, and no systematic reviews consolidating this literature have been published. The purpose of this article, then, is to facilitate the continued growth of this field by examining the characteristics of CAPs and the current state of the science, identifying the facilitating and hindering influences on the collaborative process, and developing a common term and conceptual definition for use across disciplines. METHODS: Our systematic search of 6 major literature databases generated 1,332 unique articles, 50 of which met our criteria for inclusion and provided data on 54 unique CAPs. We then analyzed studies to describe CAP characteristics and to identify the terms and methods used, as well as the common influences on the CAP process and distal outcomes. FINDINGS: CAP research spans disciplines, involves a variety of community stakeholders, and focuses on a large range of study topics. CAP research articles, however, rarely report characteristics such as membership numbers or duration. Most studies involved case studies using qualitative methods to collect data on the collaborative process. Although various terms were used to describe collaborative partnerships, few studies provided conceptual definitions. Twenty-three facilitating and hindering factors influencing the CAP collaboration process emerged from the literature. Outcomes from the CAPs most often included developing or refining tangible products. CONCLUSIONS: Based on our systematic review, we recommend using a single term, community-academic partnership, as well as a conceptual definition to unite multiple research disciplines. In addition, CAP characteristics and methods should be reported more systematically to advance the field (eg, to develop CAP evaluation tools). We have identified the most common influences that facilitate and hinder CAPs, which in turn should guide their development and sustainment.

The association between familial ASD diagnosis, autism symptomatology and developmental functioning in young children.

Few studies have directly compared individuals with and without a relative diagnosed with ASD on various domains. The present study aimed to examine the relationship between familial ASD diagnosis and the exhibition of ASD symptoms in young children with and without ASD diagnoses. Participants included 8353 children aged 17-37 months old and their families. They were divided into four groups based on individual and family diagnosis, then compared on autism symptomatology and developmental domains. No differences were found between ASD groups on overall scores and each of the factor domains, indicating no association between family ASD diagnosis and ASD symptomatology or developmental functioning. Disparate results were found for atypically developing groups with and without relatives diagnosed with ASD. Implications of these results are discussed.

Long-Term Treatment Outcomes of PEERS® for Preschoolers: A Parent-Mediated Social Skills Training Program for Children with Autism Spectrum Disorder.

Although parent-assisted social skills interventions may reduce early social challenges in preschool-aged children with autism spectrum disorder (ASD), limited research has explored whether intervention gains maintain several years after treatment. This study examined the durability of PEERS® for Preschoolers, a parent-mediated social skills training program for preschool-aged children with ASD and other social challenges. Twenty-nine parents reported on child and family outcomes 1-5 years following treatment. Results demonstrated maintenance of treatment gains on measures of ASD-related social impairments including social communication, social responsiveness, social motivation, and peer engagement. Post-treatment improvements in problem behaviors and parenting stress were not maintained at long-term follow-up. Implications of these results are discussed.

Efficacy of PEERS® for Adolescents via Telehealth Delivery.

PEERS® for Adolescents is an evidence-based social skills intervention for autistic youth and adolescents with other social challenges. The efficacy and effectiveness of PEERS® are well established; however, limited data on PEERS® via telehealth delivery exist. The current study aimed to examine the efficacy of PEERS® for Adolescents via telehealth and compare outcomes between telehealth and in-person modalities. Thirty-one adolescents (Mage = 13.77, SD = 2.14) participated in telehealth groups, and outcomes were compared with 212 adolescents (Mage = 14.02, SD = 2.00) from in-person groups. Findings demonstrate PEERS® for Adolescents via telehealth results in significant improvements in social skills knowledge, social responsiveness, overall social skills and problem behaviors, and social engagement. Telehealth outcomes are relatively equivalent to in-person delivery.