RESUMO
Analysis of genomic DNA methylation by generating epigenetic signature profiles (episignatures) is increasingly being implemented in genetic diagnosis. Here we report our experience using episignature analysis to resolve both uncomplicated and complex cases of neurodevelopmental disorders (NDDs). We analyzed 97 NDDs divided into (1) a validation cohort of 59 patients with likely pathogenic/pathogenic variants characterized by a known episignature and (2) a test cohort of 38 patients harboring variants of unknown significance or unidentified variants. The expected episignature was obtained in most cases with likely pathogenic/pathogenic variants (53/59 [90%]), a revealing exception being the overlapping profile of two SMARCB1 pathogenic variants with ARID1A/B:c.6200, confirmed by the overlapping clinical features. In the test cohort, five cases showed the expected episignature, including (1) novel pathogenic variants in ARID1B and BRWD3; (2) a deletion in ATRX causing MRXFH1 X-linked mental retardation; and (3) confirmed the clinical diagnosis of Cornelia de Lange (CdL) syndrome in mutation-negative CdL patients. Episignatures analysis of the in BAF complex components revealed novel functional protein interactions and common episignatures affecting homologous residues in highly conserved paralogous proteins (SMARCA2 M856V and SMARCA4 M866V). Finally, we also found sex-dependent episignatures in X-linked disorders. Implementation of episignature profiling is still in its early days, but with increasing utilization comes increasing awareness of the capacity of this methodology to help resolve the complex challenges of genetic diagnoses.
RESUMO
Sexual assault has come to the forefront in terms of prevention and education for many social institutions such as college campuses. However, with a growing body of research highlighting the importance and effectiveness of interventions, research examining the impact of sexual assault education (SAE) on altering rape myth acceptance (RMA) among nonstudent populations is severely lacking. This is particularly problematic when considering that the issue of sexual assault extends well beyond academia in the United States. Accordingly, this study aims to fill this gap by employing an experimental design with repeated measures. Using a sample of 137 nonstudents surveyed via Amazon's Mechanical Turk, participants were randomly assigned to a treatment (rape myth intervention) or control (unrelated video content) group. To detect changes in RMA after a short rape myth education intervention, pretest and posttest RMA scores were generated for all participants using an altered version of the Updated Illinois Rape Myth Adherence scale. The treatment video was roughly 10 min in length and constructed by the lead author for the current research. All participants were presented with common rape myths, and then, the treatment group was provided with information (e.g., available research and statistics) to "debunk" these myths, and ultimately decrease acceptance of myths. Analyses indicate support for a significant change in RMA scores from pretest to posttest in the treatment group, finding support for the use of informal rape myth education in altering immediate RMA scores of a nonstudent sample. The RMA difference scores were also examined through a demographic lens to determine if the inclusion could further explain score changes. Demographics were not deemed significant predictors. Limitations and implications are discussed.
