As with all fields of medicine, the first step toward medical management of genetic disorders is obtaining an accurate diagnosis, which often requires testing at the molecular level. Unfortunately, given the large number of genetic conditions without a specific intervention, only rarely does a genetic diagnosis alter patient management-which raises the question, what is the added value of obtaining a molecular diagnosis? Given the fast-paced advancement of genomic technologies, this is an important question to address in the context of genome-scale testing. Here, we address the value of establishing a diagnosis using genome-scale testing and highlight the benefits and drawbacks of such testing. We also review and compare recent major studies implementing genome-scale sequencing methods to identify a molecular diagnosis in cohorts manifesting a broad range of Mendelian monogenic disorders. Finally, we discuss potential future applications of genomic sequencing, such as screening for rare conditions.
Keywords: clinical diagnostics; genomic medicine; monogenic disorders; next-generation sequencing; whole-exome sequencing; whole-genome sequencing.