Advances in genomic analysis technologies have expanded the application of genetic testing in the diagnosis of rare diseases. Although genome analyses can identify nucleotide sequence variations, in Japan only licensed physicians are authorized to integrate these findings with clinical data and render diagnostic judgments. Commercial laboratories may provide analytical results but are not permitted to offer diagnostic interpretations.
Accurate diagnosis requires comprehensive expertise in gene structure analysis, human genetics, and disease-specific pathophysiology. However, genetic testing provides information primarily at the molecular level, and establishing causal relationships between genetic variants and clinical phenotypes remains challenging.
In this lecture, I will first outline the status and technical limitations of genetic testing and discuss the principles for interpreting standard genetic testing reports. I will then introduce currently available approaches for correlating structural genetic variants with clinical phenotypic manifestations.
In immunodeficiency disorders, including those with autoinflammatory features, genetic testing alone often fails to yield definitive diagnostic conclusions. These conditions involve complex and dynamic immune networks, which limit the utility of genetic testing as a standalone diagnostic tool. Consequently, definitive diagnosis frequently requires not only validated clinical laboratory assays but also complementary insights derived from research-based investigations.
Integration of routine clinical testing with emerging research findings is essential for improving diagnostic accuracy. This lecture aims to provide a framework for understanding the appropriate use and limitations of genetic testing, thereby contributing to more accurate and definitive diagnoses of immunodeficiency disorders.
