Recent Advances in the Clinical Application of Next-Generation Sequencing

Next-generation sequencing (NGS) technologies have changed the process of genetic diagnosis from a gene-by-gene approach to syndrome-based diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS). A priori information on the causative genes that might underlie a genetic condition is a prerequisite for genetic diagnosis before conducting clinical NGS tests. Theoretically, DPS, DES, and DGS do not require any information on specific candidate genes. Therefore, clinical NGS tests sometimes detect disease-related pathogenic variants in genes underlying different conditions from the initial diagnosis. These clinical NGS tests are expensive, but they can be a cost-effective approach for the rapid diagnosis of rare disorders with genetic heterogeneity, such as the glycogen storage disease, familial intrahepatic cholestasis, lysosomal storage disease, and primary immunodeficiency. In addition, DES or DGS may find novel genes that that were previously not linked to human diseases.