The number of variants detected using Exome Diagnostics is very high. To accelerate and focus the interpretation of the results, the symptoms of the patients are recorded with as much precision and detail as possible. A team of experts and human geneticists create an individual list of candidate genes that are known to be associated with the symptoms of the patient with the help of the Human Phenotype Ontology (HPO). In the context of single Exome Diagnostics, detected variants within candidate genes are evaluated and the results and interpretation are summarized in a medical report that is returned to the treating physician.
Trio Exome Diagnostics is a powerful way to identify causative variants. The parents of the patient are also tested and an exome-wide segregation analysis is performed. This allows variants to be filtered and non-pathogenic variants to be eliminated. Reports in the literature demonstrate a significant increase in diagnostic detection rates, from 21% for single Exome Diagnostics to 37% for Trio Exome Diagnostics (Farwell, 2015). The higher detection rates are achieved because Trio Exome Diagnostics:
- enables the better identification and interpretation of genes and variants that are not known to be clinically associated with the disease, and
- crucially, improves the detection of causative mutations which are frequently new (de novo) in the patient.
Trio Exome Diagnostics is particularly time- and cost effective, because the number of variants to evaluate is minimized, and the numerous segregation analyses of single variants, necessary when using Sanger sequencing, are avoided.
To perform (Trio) Exome Diagnostics, the patient (and possibly relatives) needs to attend genetic counseling according the German Gendiagnostikgesetz (GenDG).