The Korean Undiagnosed Diseases Program Phase I: Expansion of the Nationwide Network and the Development of Long-term Infrastructures

Abstract

Background: Phase I of the Korean Undiagnosed Diseases Program (KUDP), which was performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructures, including a data management system and functional core laboratory, for long-term translational research. Herein, we shared the clinical experiences of the Phase I program and introduced the activities of the functional core laboratory and data management system.Results: During the program (2018-2020), 458 patients were finally enrolled and classified into 3 groups according to the following criteria: I) those with a specific clinical diagnosis that required direct testing first (32 patients); II) those with a clinical diagnosis with genetic and phenotypic heterogeneity (353 patients); and III) those with atypical presentations or unknown diseases thus far (73 patients). All patients underwent individualized diagnostic processes by the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were finally diagnosed with nongenetic disorders. The KUDP functional core laboratory with a group of experts organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Among the 40 genes without identified causality for human Mendelian disorders to date, six different genes are on track for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, expecting reinforcement of the nationwide clinical network and further international collaboration.Conclusions: The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructures for a data sharing system and functional research. The advancement of the KUDP may initiate sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.