Faculty Bibliography

PURPOSE/OBJECTIVE:SET is a member of the inhibitor of histone acetyltransferases (INHAT) complex, involved in transcriptional silencing and gene regulation. Pathogenic variants in SET are postulated to cause neurodevelopmental disorder (NDD) phenotypes, but as only few individuals are described, detailed clinical information is scarce. Hence, currently counseling on phenotype and prognosis of this condition remains challenging. METHODS:Here we describe the clinical phenotype and mutational spectrum of 23 unreported individuals harboring (likely) pathogenic variants in SET. RESULTS:Phenotypes include global developmental delay with often pronounced hypotonia, delayed motor development and speech and language delay, ultimately evolving into (mild) intellectual disability. Comorbidities include behavioral concerns, sleeping disturbance and variable unspecific ocular problems. Next generation computer-assisted phenotyping using GestaltMatcher showed limited overlapping facial features between affected individuals and differences compared to disorders caused by related chromatin modifying genes. In addition, we generated a DNA methylation signature, able to distinguish individuals carrying pathogenic variants in SET from individuals with other NDDs and healthy controls. We used this DNA methylation signature to assess pathogenicity of two variants of uncertain significance in SET found in two additional individuals. CONCLUSION/CONCLUSIONS:Together, this expands the knowledge on the SET-related disorder and provides novel approaches for its diagnosis.

After decades of efforts by academic and professional organizations and by governmental agencies to promote advance care planning, less than half of adults in the USA have formally executed advance directives. For patients who have completed these documents, studies find limited impact on end-of-life care. In this paper, we discussed ways in which bias towards certain values in the health care enterprise including ethnocentrism, the centering of one set of cultural norms, may contribute to the public's ambivalence and the relative inefficacy of advance directives. We offer a more expansive perspective on this aspect of clinical care with the goal of serving all patients more effectively.

Health disparities are primarily driven by structural inequality including systemic racism. Medical educators, led by the AAMC, have tended to minimize these core drivers of health disparities. Instead, it has adopted a culture-based agenda through the framework of cultural competence to address disparities despite a paucity of supporting data. Cultural competence is ethnocentric in orientation and its content sustains biases that are long-standing in health care. Moreover, Cultural competence is based on a number of flawed assumptions and is not structured around a set of clearly stated ethical values. In this paper, we will demonstrate ways in which Cultural competence reflects embedded ethnocentrism, perpetuates entrenched biases, and fails to recognize the depth and breadth of systemic racism as these relate to the stated goal of Cultural competence-the mitigation of health disparities. In addition, we offer a reframed approach to health disparities in medical education.