Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation

Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes.

We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology.