Undiagnosed rare disease clinic identifies a novel UBE3A variant in two sisters with Angelman syndrome: The end of a diagnostic odyssey.

Angelman syndrome (AS, MIM #105830) is a neurodevelopmental disorder characterized by severe intellectual disability, profound developmental delay, movement or balance problems, an excessively cheerful disposition, and seizures. AS results from inadequate expression of the maternal UBE3A gene (MIM #601623), which encodes an E3 ligase in the ubiquitin-proteasome pathway. Here we present the case of two sisters with features consistent with AS who had negative methylation analyses. An autism/intellectual disability expanded panel revealed a maternally inherited novel UBE3A (NM_001354506.2) variant c.2443C>T p.(Pro815Ser) in both patients that was initially classified as a variant of uncertain significance. The patients were enrolled in Indiana University's Undiagnosed Rare Disease Clinic (URDC) to further investigate the variant. Additional data, including deep phenotyping, familial segregation analysis, and in silico studies, suggest that the variant is likely pathogenic. 3D modeling studies based on the available crystal structure revealed that the Pro815Ser variant can introduce more flexibility into the protein and alter its enzymatic activity. Recent literature confirms the pathogenic nature of the variant. Reanalysis of the UBE3A variant has heightened existing knowledge of AS and has offered this family an end to their diagnostic odyssey.

Experience conducting a community-engaged student research project involving an underrepresented community: A reflective essay.

Recruiting racially and ethnically underrepresented participants into genetics research studies has been challenging. While many institutions have taken steps to address the inequity in genetics research, genetic counseling training programs have the chance to inspire students to engage with underrepresented communities through utilizing different research methodologies. These methodologies can help students focus on research projects that increase access to genetics services and improve clinical care. Community-engaged research (CER) presents a pedagogical approach to enhance service-learning opportunities for students. Furthermore, it allows students to develop practical research skills for doing research with the community, rather than on the community. CER is a collaborative community-academic partnership that leads to mutual benefit and outcomes such as inclusion and engagement of the community in research, building trust and relationships, and increasing cultural awareness and exposure. In addition, CER can be used to address research and healthcare inequities by providing opportunities for genetics professionals and trainees to work closely with underrepresented populations. We aim to highlight the opportunities CER provides to students, mentors, and faculty within the context of graduate research in genetic counseling training from the experiences of a student and an educator. In addition, we hope to emphasize the necessity for projects like these to address the gaps in participation of underrepresented patient populations in research and identify areas that are mutually beneficial to improve health outcomes, patient care experiences, access, and service delivery. This reflective essay illustrates the completion of a CER project that was developed in collaboration with community members to address gaps in clinical genetics services in Indigenous healthcare.

Using a family history intervention to improve cancer risk perception in a black community.

Few studies examine the use of family history to influence risk perceptions in the African American population. This study examined the influence of a family health history (FHH) intervention on risk perceptions for breast (BRCA), colon (CRC), and prostate cancers (PRCA) among African Americans in Pittsburgh, PA. Participants (n = 665) completed pre- and post-surveys and FHHs. We compared their objective and perceived risks, classified as average, moderate, or high, and examined the accuracy of risk perceptions before and after the FHH intervention. The majority of participants had accurate risk perceptions post-FHH. Of those participants who were inaccurate pre-FHH, 43.3%, 43.8%, and 34.5% for BRCA, CRC, and PRCA, respectively, adopted accurate risk perceptions post-FHH intervention. The intervention was successful in a community setting. It has the potential to lead to healthy behavior modifications because participants adopted accurate risk perceptions. We identified a substantial number of at-risk individuals who could benefit from targeted prevention strategies, thus decreasing racial/ethnic cancer disparities.

The use of family health histories to address health disparities in an African American community.

African Americans continue to suffer from health disparities. The Center for Minority Health (CMH) within the University of Pittsburgh has the mission to eliminate racial and ethnic health disparities. CMH has designed and implemented the Family Health History (FHH) Initiative. The FHH Initiative places genetic-counseling graduate students in the African American community to provide risk assessments and emphasize the importance of family history as it pertains to disease prevention. The FHH Initiative also allows participants to enroll into the Minority Research Recruitment Database (MRRD). This enables CMH to alert individuals to available research participation opportunities. In the first year of this program, 225 African Americans completed their family health histories. More than 60% of individuals enrolled in the MRRD. The authors report their initial successes and challenges of an initiative that incorporates awareness of family history information, proper screening guidelines, behavior-modification recommendations, and support for participation in clinical research.