Exome sequencing can be used to diagnose the genetic cause of disease in a patient. Identification of the underlying disease gene mutation(s) can have major implications for diagnostic and therapeutic approaches, can guide prediction of disease natural history, and makes it possible to test at-risk family members. There are many factors that make exome sequencing superior to single gene analysis including the ability to identify mutations in genes that were not tested due to an atypical clinical presentation or the ability to identify clinical cases where mutations from different genes contribute to the different phenotypes in the same patient.
Having diagnosed a genetic cause of a disease, this information may guide the selection of appropriate treatment. The first time this strategy was performed successfully in the clinic was in the treatment of an infant with inflammatory bowel disease. A number of conventional diagnostics had previously been used, but the results could not explain the infants symptoms. Analysis of exome sequencing data identified a mutation in the XIAP gene. Knowledge of this genes function guided the infant's treatment, leading to a bone marrow transplantation which cured the child of disease.
Researchers have used exome sequencing to identify the underlying mutation for a patient with Bartter Syndrome and congenital chloride diarrhea. Bilgular's group also used exome sequencing and identified the underlying mutation for a patient with severe brain malformations, stating "[These findings] highlight the use of whole exome sequencing to identify disease loci in settings in which traditional methods have proved challenging... Our results demonstrate that this technology will be particularly valuable for gene discovery in those conditions in which mapping has been confounded by locus heterogeneity and uncertainty about the boundaries of diagnostic classification, pointing to a bright future for its broad application to medicine".
Researchers at University of Cape Town, South Africa used exome sequencing to discover the genetic mutation of CDH2 as the underlying cause of a genetic disorder known as arrhythmogenic right ventricle cardiomyopathy (ARVC)‚ which increases the risk of heart disease and cardiac arrest. [https://www.news.uct.ac.za/article/-2017-03-10-uct-researchers-discover-heart-attack-gene]