Abstract: There are ~7000 recognized rare diseases, which affect 5 - 10% of the U.S. population. The Undiagnosed Disease Network (UDN) is motivated by the dual goals of providing a diagnosis to patients who have undergone a protracted unsuccessful diagnostic odyssey and by the opportunities for scientific discovery that these unique patients offer. The UDNs impact also extends to systematizing the diagnostic approach to the undiagnosed patient. Our Pacific Northwest UDN site has served our region, and recently much of the Western United States, bringing a conclusion to the journey of our patients. Our group has deep and broad expertise across all the relevant areas required for the evaluation and diagnosis of adult and pediatric patients who have had a previously unproductive clinical odyssey, to identify novel disorders, and to advance the broader goals of the UDN. Foremost, we have a diverse team of physicians and an established record in the characterization of new genetic disorders and the identification of their genetic mechanisms. We leverage our unique existing regional medical and educational infrastructure, unique genomic strengths, and providers in the states of Washington, Wyoming, Alaska, Montana, and Idaho to identify patients in need and provide regional care. Our clinicians include members with nationally recognized expertise in neurogenetics, adult and pediatric genetics/genomics, immunology, internal medicine, pediatrics, neurology, teratology, human development, dysmorphology, and neonatology. We have national expertise in genomic sequencing and annotation, copy number variant technology, data-sharing, clinical informatics, bioethics, molecular diagnostic testing, and statistical genetics; covering disciplines such as: bioethics, pharmacogenetics, genomics, environmental genetics, translational bioinformatics, health care outcomes, and policy. We serve a critical regional need. The Specific Aims are: Aim1: Provide broad expert diagnostic services, including detailed phenotyping, to determine the cause of and treatment options for any undiagnosed diseases in adults and children, focusing on those who are under- or non-insured or otherwise medically under-served, with a plan towards sustainability. Aim 2: Provide unique national expertise to enhance clinical and discovery capabilities and facilitate UDN disease discovery and knowledge dissemination.

Narrative The application of genomics and other specialized evaluation to diagnosis rare human disorders, has been centered in major medical centers. The Undiagnosed Disease Network (UDN) extends the reach of rare disease evaluation and diagnosis by providing access to the undiagnosed patient in all communities. We propose an additional year of funding for the Pacific Northwest Undiagnosed Diseases Network Clinic (PNW UDN) site to further the goals of the UDN and to provide UDN access for under- or non-insured participants in the Pacific Northwest.