Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis

Abstract 362: Comparison of Mig-6 and hormone receptor expression to BMI as predictors of responsiveness to progestin therapy for endometrial hyperplasia and cancer

Abstract Objectives: Mitogen-inducible gene 6 (Mig-6) is an immediate early response gene that can be induced by stressful stimuli and mitogens, including hormones and growth factors. Ablation of Mig-6 leads to epithelial hyperplasia and adenocarcinomas in a variety of organs, including the endometrium. Mig-6 has been identified as a downstream target of the progesterone receptor (PR) in the uterus. Thus, our goal was to compare Mig-6 and hormone receptor expression to BMI as predictors of responsiveness to progestin therapy for endometrial hyperplasia and cancer. Methods: Women were identified who underwent progestin treatment (oral or IUD) for either endometrial hyperplasia or cancer. Expression of Mig-6 and the hormone receptors, G-protein coupled receptor 30 (GPR30), estrogen receptor (ER) and PR were evaluated by immunohistochemistry (IHC) in 58 paired formalin-fixed, paraffin-embedded endometrial biopsy specimens before and after progestin treatment. Tissue microarrays were constructed, and three cores were analyzed for each patient. IHC staining was scored according to the intensity (1+ to 3+) and qualitative percent cells staining per core. A “histoscore” was calculated, based on multiplying these two determinants ranging from 0 to 300 (i.e. intensity x % labeled). Results were analyzed using the Student t-test and ANOVA. Results: There were 41 responders to progestin therapy and 17 non-responders. The majority had endometrial hyperplasia (56/58) but 2 women had grade I endometrial carcinomas. The BMI between the two groups was statistically different at 40.2 for the responders and 49.9 for the non-responders (p=0.0008). There was no difference in age or ER/PR status between the two groups. Mig-6 expression prior to treatment did not predict response to progestin therapy (183.5 = responders, 196.6 = non-responders, p=0.47). GPR30 expression prior to progestin treatment was 118.8 for the responders and 68.9 for the non-responders but was not statistically significant (p=0.06). Neither post-treatment Mig-6 (179.1 = responders, 204.0 = non-responders) or GPR30 (103.6 = non-responders, 108.6 = responders) histoscores or change in histoscores pre- and post-treatment predicted response to progestin therapy. Conclusions: BMI but not Mig-6 expression or hormone receptor expression predicted response to progestin therapy in women with endometrial hyperplasia and cancer. GPR30 may have potential as a biomarker of progestin responsiveness but needs to be evaluated in a larger cohort of women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 362. doi:10.1158/1538-7445.AM2011-362</jats:p

A Survey of Incivility in the OT Workplace

Abstract Date Presented 04/13/21 Incivility in health care has adverse effects on patient care coordination, patient outcomes, practitioner well-being, and organizational costs. This study examined the relationships between perceived incivility and practitioners’ demographics, workplace factors, and resilience. The highest rates of incivility were reported by practitioners with 2–10 years of experience, working in skilled-nursing or long-term care, and with lowest resilience. Practices for mitigating incivility are discussed. Primary Author and Speaker: Deborah J. Bolding Contributing Authors: Taniya Varughese, Allison King</jats:p

Incivility in the Occupational Therapy Workplace: A Survey of Practitioners

Abstract Importance: Incivility in health care settings has detrimental effects on practitioners’ well-being, patient outcomes, and health care costs. Objective: To explore the prevalence and types of perceived incivility experienced by occupational therapy practitioners in their workplaces and the relationships between perceived incivility and practitioner demographics. Design: Cross-sectional, online survey. Setting: Surveys were posted to occupational therapy social media sites. Participants: Occupational therapy practitioners throughout the United States. Outcomes and Measures: The Negative Acts Questionnaire–Revised (NAQ–R) was used to measure incivility and bullying. Participants answered demographic questions, and one-way analyses of variance and t tests were used to examine differences between demographic characteristics and mean scores on the NAQ–R. Results: A total of 1,320 practitioners completed the survey. Although the incidence of incivility was low compared with prior research in other health professions, 11% of respondents reported being victims of bullying in the workplace. Practitioners with less experience and who worked in long-term care and skilled nursing settings were more likely to experience incivility, and occupational therapy practitioners experienced significantly less incivility than occupational therapy assistants. Conclusions and Relevance: Practitioners, colleagues, managers, and organizations must collaborate to foster an environment of civility and respect to mitigate the effects of incivility on patient outcomes, practitioners’ well-being, and health care costs. What This Article Adds: This survey provides baseline information regarding incivility experienced by occupational therapy practitioners, an important first step in developing evidence-based interventions to promote safe and healthy workplaces.</jats:p

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

International audienc

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Accepted version (6 month embargo), submitted versio