Medical care of rare and undiagnosed diseases: Prospects and challenges.

Rare and undiagnosed diseases tend to be diverse, misdiagnosed, and difficult to diagnose. In some cases, the disease is progressive and life-threatening. Yet, to date, an estimated 95% of rare diseases have no approved therapy. Therefore, rare and undiagnosed diseases are considered the ultimate challenges for understanding human diseases. Here, we review the research progress, research frontiers, and important scientific issues related to rare and undiagnosed diseases. We mainly focus on five topics: (1) the identification and functional analysis of disease-causing genes; (2) the construction of cells, organoids, and animal models for mechanism validation; (3) subtyping and diagnosis; (4) treatment and drug screening based on causative genes and mutations; and (5) new technologies and methods for studying rare and undiagnosed diseases. In this review, we briefly update and discuss the pathogenic mechanisms and precision medicine for rare and undiagnosed diseases.