Podcast: #thisisanautismmentalhealthcrisis
The prevalence of autism spectrum disorders (ASD) and the number of identified ASD-related genes have increased in recent years. The SETD5 gene encodes a SET-containing-domain 5 protein, a likely reader enzyme. Genetic evidences suggest that SETD5 malfunction contributes to ASD phenotype, such as on intellectual disability (ID) and facial dysmorphism. In this review, we mapped the clinical phenotypes of individuals carrying mutations on the SETD5 gene that are associated with ASD and other chromatinopathies (mutation in epigenetic modifiers that leads to the development of neurodevelopmental disorders such as ASD). After a detailed systematic literature review and analysis of public disease-related databank, we found so far 42 individuals carrying mutations on the SETD5 gene, with 23.8% presenting autistic-like features. Furthermore, most of mutations occurred between positions 9,480,000-9,500,000 bp on chromosome 3 (3p25.3) at the SETD5 gene locus. In all males, mutations in SETD5 presented high penetrance, while in females the clinical phenotype seems more variable with two reported cases showing normal female carriers and not presenting ASD or any ID-like symptoms. At the molecular level, SETD5 interacts with proteins of PAF1C and N-CoR complexes, leading to a possible involvement with chromatin modification pathway, which plays important roles for brain development. Together, we propose that mutations on the SETD5 gene could lead to a new syndromic condition in males, which is linked to 3p25 syndrome, and can leads to ASD-related intellectual disability and facial dysmorphism. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 500-518, 2018.
Keywords: SETD5 gene; SETD5 syndrome; autism spectrum disorder; genetic variants; intellectual disability; syndromic autism.
The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.
Access to early intensive behavioral intervention for children with autism spectrum disorder is commonly recommended. Intervention programs may include high rates of instructional trials, which may evoke escape-maintained problem behavior. Recent research on “pairing” or “rapport-building” interventions have sought to reduce the likelihood that problem behavior occurs during instruction using antecedent manipulations. The current study evaluated a structured intervention that included differential reinforcement and demand fading to increase participants’ response allocation to instructional settings without the use of physical guidance. Nine minimally verbal girls under the age of 6 years with autism spectrum disorder enrolled in the study. The protocol was effective for seven of the nine participants. One participant did not complete the protocol due to competing behavior and an additional participant did not require the intervention. Our findings suggest that the structured intervention was effective in increasing appropriate behavioral repertoires that are necessary for children with autism spectrum disorder to effectively benefit from early educational programs.
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined and diagnosed by core deficits in social communication and the presence of restricted and repetitive behaviors. Research on face processing suggests deficits in this domain in ASD but includes many mixed findings regarding the nature and extent of these differences. The first eye movement to a face has been shown to be highly informative and sufficient to achieve high performance in face identification in neurotypical adults. The current study focused on this critical moment shown to be essential in the process of face identification.
Methods: We applied an established eye-tracking and face identification paradigm to comprehensively characterize the initial eye movement to a face and test its functional consequence on face identification performance in adolescents with and without ASD (n = 21 per group), and in neurotypical adults. Specifically, we presented a series of faces and measured the landing location of the first saccade to each face, while simultaneously measuring their face identification abilities. Then, individuals were guided to look at specific locations on the face, and we measured how face identification performance varied as a function of that location. Adolescent participants also completed a more traditional measure of face identification which allowed us to more fully characterize face identification abilities in ASD.
Results: Our results indicate that the location of the initial look to faces and face identification performance for briefly presented faces are intact in ASD, ruling out the possibility that deficits in face perception, at least in adolescents with ASD, begin with the initial eye movement to the face. However, individuals with ASD showed impairments on the more traditional measure of face identification.
Conclusion: Together, the observed dissociation between initial, rapid face perception processes, and other measures of face perception offers new insights and hypotheses related to the timing and perceptual complexity of face processing and how these specific aspects of face identification may be disrupted in ASD.
Keywords: Autism spectrum disorder; Eye gaze; Face identification.
The aim of this study is to holistically synthesise the extent and range of literature relating to the employment of individuals with autism spectrum disorder. Database searches of Medline, CINAHL, PsychINFO, Scopus, ERIC, Web of Science and EMBASE were conducted. Studies describing adults with autism spectrum disorder employed in competitive, supported or sheltered employment were included. Content analysis was used to identify the strengths and abilities in the workplace of employees with autism spectrum disorder. Finally, meaningful concepts relating to employment interventions were extracted and linked to the International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder. The search identified 134 studies for inclusion with methodological quality ranging from limited to strong. Of these studies, only 36 evaluated employment interventions that were coded and linked to the International Classification of Functioning, Disability and Health, primarily focusing on modifying autism spectrum disorder characteristics for improved job performance, with little consideration of the impact of contextual factors on work participation. The International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder are a useful tool in holistically examining the employment literature for individuals with autism spectrum disorder. This review highlighted the key role that environmental factors play as barriers and facilitators in the employment of people with autism spectrum disorder and the critical need for interventions which target contextual factors if employment outcomes are to be improved.
Keywords: adult; intervention; strengths-based; vocational rehabilitation; work environment.