De novo germline mutations in the RNA helicase DDX3X account for 1%–3% of unexplained intellectual disability (ID) cases in females and are associated with autism, brain malformations, and epilepsy. ...Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here, we use human and mouse genetics and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development. We report the largest clinical cohort to date with DDX3X mutations (n = 107), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcomes. We show that Ddx3x controls cortical development by regulating neuron generation. Severe DDX3X missense mutations profoundly disrupt RNA helicase activity, induce ectopic RNA-protein granules in neural progenitors and neurons, and impair translation. Together, these results uncover key mechanisms underlying DDX3X syndrome and highlight aberrant RNA metabolism in the pathogenesis of neurodevelopmental disease.
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•Discovery of 107 mutations in the RNA helicase DDX3X causing cortical malformations•Clinical severity is linked to reduced helicase activity and RNA-protein granules•Ddx3x is required in neural progenitors to produce cortical neurons during development•Severe missense mutations cause polymicrogyria and impair translation of targets
Using human and mouse genetics, Lennox et al. identify 107 mutations in DDX3X, demonstrating DDX3X is essential for cortical development. A striking correlation between the severity of clinical mutations and abnormal RNA metabolism highlights unappreciated mechanisms of DDX3X syndrome.
RNA molecules rely on proteins across their life cycle. DDX3X encodes an X-linked DEAD-box RNA helicase with a Y-linked paralog, DDX3Y. DDX3X is central to the RNA life cycle and is implicated in ...many conditions, including cancer and the neurodevelopmental disorder DDX3X syndrome. DDX3X-linked conditions often exhibit sex differences, possibly due to differences between expression or function of the X- and Y-linked paralogs DDX3X and DDX3Y. DDX3X-related diseases have different mutational landscapes, indicating different roles of DDX3X. Understanding the role of DDX3X in normal and disease states will inform the understanding of DDX3X in disease. We review the function of DDX3X and DDX3Y, discuss how mutation type and sex bias contribute to human diseases involving DDX3X, and review possible DDX3X-targeting treatments.
RNA molecules rely on proteins across their life cycle. DDX3X encodes an X-linked DEAD-box RNA helicase with a Y-linked paralog, DDX3Y. DDX3X is central to the RNA life cycle and is implicated in many conditions, including cancer and the neurodevelopmental disorder DDX3X syndrome. DDX3X-linked conditions often exhibit sex differences, possibly due to differences between expression or function of the X- and Y-linked paralogs DDX3X and DDX3Y. DDX3X-related diseases have different mutational landscapes, indicating different roles of DDX3X. Understanding the role of DDX3X in normal and disease states will inform the understanding of DDX3X in disease. We review the function of DDX3X and DDX3Y, discuss how mutation type and sex bias contribute to human diseases involving DDX3X, and review possible DDX3X-targeting treatments.
DDX3X and DDX3Y have similar structures and functions but their expression differs. Differences between the paralogs can lead to sex differences in development and disease.DDX3X and DDX3Y are dose sensitive in development and disease. Low levels of DDX3X lead to developmental perturbations and disease. Overexpression of DDX3X can also lead to disease.DDX3X and DDX3Y have different roles in different cancers, which can change as cancer progresses. These differences can contribute to sex differences in cancer incidence and severity.Germline DDX3X mutations can lead to intellectual disability (ID) through perturbed neurogenesis. The mutations’ impacts can vary by sex and severity.Males and females display different patterns in DDX3X-related cancer and ID. In many cancers, males have more premature termination codon (PTC)-inducing somatic DDX3X mutations, while in ID, only females have germline PTC-inducing mutations.
The SSIS SEL Brief Scales (SSIS SEL
b
) are multi-informant (teacher, parent, and student) measures that were developed to efficiently assess the SEL competencies of school-age youth in the United ...States. Recently, the SSIS SEL
b
was translated into multiple languages for use in a multi-site study across six European countries (Croatia, Greece, Italy, Latvia, Portugal, and Romania). The purpose of the current study was to examine concurrent and predictive evidence for the SEL Composite scores from the translated versions of the SSIS SEL
b
Scales. Results indicated that SSIS SEL
b
Composite scores demonstrated expected positive concurrent and predictive relationships with scores from the Connor-Davidson Resilience Scale (CD-RISC) and negative relationships with scores from the problem behavior scales of the Strengths and Difficulties Questionnaire (SDQ). Although there were a few exceptions, these patterns generally were consistent across informants (parents, teachers, and students) and samples providing initial validity evidence for the Composite score from the translated versions of the SSIS SEL
b
Scales. Limitations and future research directions are discussed.
Introduction
Despite increasing interest in measuring social and emotional learning (SEL), there is a lack of European-validated tools for assessing the efficacy of SEL programs. The aim of this ...study was to validate an Italian version of the social skills improvement system (SSIS) SEL brief scales–student form.
Methods
Participants were 1,175 students (mean age: 11.02 years; SD: 2.42; range: 8–16 years; males: 46.8%) recruited at schools in Northern Italy.
Statistical analyses and results
Initial confirmatory factor analysis encountered a series of challenges, implying non-convergence of the original five-factor measurement model (self-awareness, self-management, social awareness, relationship skills, and responsible decision-making) based on the Collaborative on Academic Social Emotional Learning (CASEL) competency framework established with students in the United States. Further exploratory and confirmatory analyses supported a four-factor model that remained partially invariant across gender groups. The Italian version of the SSIS SEL brief scales was thus shown to be an efficient measurement tool for estimating social and emotional learning in students.
Discussion
We discuss the implications of findings in relation to selecting valid and reliable instruments for assessing children’s and adolescents’ SEL competencies, while considering the culturally-situated nature of the constructs under study.
In this retrospective commentary on “Acceptability of Behavioral Interventions Used in Classrooms: The Influence of Amount of Teacher Time, Severity of Behavior Problem, and Type of Intervention,” I ...first examine the concept of social validity and related measurement challenges per Wolf’s concerns about consumers’ subjective reactions to behavior intervention procedures. I claim the genesis of the treatment acceptability research that others and I have completed was primarily motivated to advance the measurement of a subjective and fundamental construct in the process of selecting and implementing interventions in classrooms with teachers and children. With this background, I briefly describe the featured school-focused treatment acceptability study, followed by inferences about its (a) impact on subsequent intervention research and (b) relationship with common behavioral consultation and health care practices. I conclude with some speculations about future acceptability research and the importance of psychologists and educators caring about the social validity of their services.
One of the most consistent findings in rating scale research with children and adolescents is the modest agreement among different informants' ratings. The present study systematically explored ...patterns of agreement among teachers, parents/caregivers, and students in domains of social skills and problem behaviors using the Social Skills Improvement System-Rating Scales (SSIS-RS;
F. M. Gresham & S. N. Elliott, 2008
). Two subsamples from the normative sample of the SSIS-RS were used. The first sample of participants consisted of 168 students who had all 3 informants (parent, teacher, and self) complete the SSIS-RS scales, which was necessary to assess agreement across different raters. The second sample consisted of 164 students who had raters in a similar or same role (father-mother, teacher-teacher). The results replicated an extensive literature showing that cross-informant agreements for social skills and problem behaviors are weak to moderate. The current study invoked multitrait-multimethod logic to interpret the correlations among raters derived from different informants and showed that the convergent validity coefficients were consistently stronger than the discriminant validity correlations. Implications for assessment practices and future research are discussed.
Base rate information is important in clinical assessment because one cannot know how unusual or typical a phenomenon is without first knowing its base rate in the population. This study empirically ...determined the base rates of social skills acquisition and performance deficits, social skills strengths, and problem behaviors using a nationally representative sample of children and adolescent ages 3-18 years. Using the national standardization sample of the Social Skills Improvement System-Rating Scales (N = 4,550) across 3 informants (teacher, parent, and student) and across 3 broad age groupings (3-5 years, 5-12 years, and 13-18 years), these base rates were computed. Results showed that the base rates for social skills acquisition deficits and problem behaviors are extremely low in the general population. Base rates for social skills performance deficits and social skills strengths were considerably higher, with students in the 5- to 12-year-old age group reporting fewer performance deficits and more social skills strengths than older children (13-18 years). Teachers and parents reported more performance deficits and fewer social skills strengths across all age groups than students in the 5- to 12-year-old age group. These results are discussed in terms of the utility of base rate information in clinical decision making.
The related constructs of opportunity to learn (OTL) and achievement growth are fundamental aspects of the current large-scale assessment and accountability system in operation in the United States. ...For purposes of this article, OTL is defined as the degree to which a teacher dedicates instructional time and content coverage to the intended curriculum objectives emphasizing high-order cognitive processes, evidence-based instructional practices, and alternative grouping formats. Both OTL and achievement growth, although frequently talked about by education policy makers and teachers, are actually difficult to measure. Much of my research, in collaboration with other colleagues, over the past decade has concerned the measurement of these constructs in ways that facilitate teachers’ understanding of them and to advance sound policies regarding the instruction and assessment of students with disabilities (SWDs). In this article, I examine both the measurement of OTL and achievement growth, share recent research on them, and outline an agenda for future research on these two important aspects of standards-based accountability systems for all students.
The authors examined the cross-informant consistency and level of agreement of ratings on the Social Skills Improvement System (SSIS) Bullying Subscale. They explored the effectiveness of using this ...set of multi-informant (i.e., teacher, parent, and student) social skills rating scales with an established record of yielding reliable and valid scores to define and measure perceptions about elementary students who bully others. The study examined a sample of 112 elementary children from the SSIS national standardization sample who each received a rating regarding the frequency of their bullying behaviors by a teacher, parent, and the student himself/herself. The results showed similar findings to the existing research. Although demonstrating some overall consistency, bullying behavior scores do differ between students and across informants supporting the importance of understanding informant variance. Students showed a difference in bullying scores across informants with scores on average increasing between informants. Teacher and parent reports provided lower ratings on bullying behavior than those provided by student self-report with overall ratings remaining consistent across informants. Higher levels of consistency existed on ratings by parents and students than by teachers and students. Teachers gave higher ratings than parents did, in particular for males. An examination of study limitations and future research concludes the report.
•Perceived bullying behavior scores varied between students and across informants.•Overall higher levels of consistency existed on ratings from parents-students than from teachers-students.•Teachers provided higher ratings than parents did, in particular for males.
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