An integrated and diverse genomic medicine program for undiagnosed diseases

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Program Director/Principal Investigator (Last, First, Middle): Shashi, Vandana Abstract The goals of this administrative supplement are for the Duke clinical site to increase the number of patients evaluated, and to continue and expand our ongoing studies to facilitate UDN participation by patients who experience health disparities (defined as living in rural medically underserved areas (MUA) and/or belonging to racial/ethnic minorities). Our aims for this supplement are: Specific Aim 1: Comprehensively evaluate seven new patients with undiagnosed diseases: After streamlined and efficient application review, all accepted patients will receive comprehensive and tailored UDN evaluations, with in-person, telehealth or hybrid evaluations. At least 40% of those enrolled will be patients with health disparities. Exploratory sub-aim 1: Prospectively ascertain patient factors pertinent to UDN application from internally referred patients and offer adaptations to facilitate their UDN application and participation. All patients who are internally referred to the UDN from Duke Health providers, will be prospectively administered surveys on practical barriers/facilitators, genomic knowledge and distrust. Additionally, for the subset of internally referred patients who belong to health disparity populations, we will have two adaptations to facilitate UDN participation: (a) after referral, if they are agreeable, the study team will discuss with the patients/families, the UDN process to address study concerns and offer assistance with the UDN application and medical record collection. (b) For all accepted patients, customized accommodations will be provided to mitigate practical barriers. Specific Aim 2: Analyze the genomic sequencing data of patients and utilize adjunct technologies to provide diagnoses and identify novel candidate genes. We will perform research analysis of the genomic sequencing data on the seven patients and relevant family members, with our phenotype-agnostic approach (especially useful to identify novel candidate genes). Recent updates to our pipeline should increase our success in identifying diagnoses and novel candidates. We will pursue RNAseq and optical genome mapping for selected GS negative cases. Specific Aim 3: Focusing on NC MUA counties, obtain PCPs’ perspectives on barriers to referral/participation in the UDN/genomic medicine for their undiagnosed patients. In partnership with the NC AHEC, we will travel to four regional AHECs in NC MUAs from which we currently receive few applications, to provide a workshop that includes an educational session on undiagnosed diseases (with continuing education credit) and an interactive discussion with the PCPs, to gather perspectives on (a) the need for genomic medicine in their practice, (b) barriers/facilitators to patient referral and participation and (c) strategies that could overcome the barriers. These data will be assessed and shared with the DMCC and the network. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page