ABSTRACT
@#The concept of “precision medicine” has been a mainstay in discourses about the future of medicine, although it was not until the completion of the Human Genome Project that genetic associations to Mendelian diseases have risen dramatically. Since genetic variations in most (85%) monogenic or oligogenic diseases reside in exons, whole-exome sequencing (WES) serves as a pivotal tool in the identification of causative variants in genodermatoses and other diseases, leading to efficient and timely diagnosis. Here, we share our current diagnosis protocol for genodermatoses using WES as a first-tier solution. Two cases are presented to demonstrate the process of identifying germline variants and one case for a somatic variant. In the first case, a germline missense mutation in COL7A1 (exon73:c.G6127A) was identified for a patient that presented with clinical symptoms of dystrophic epidermolysis bullosa (DEB). Immunofluorescence study revealed decreased collagen VII expression in the dermal-epidermal junction. In case 2, we detected a germline missense mutation in KRT16 (exon1:c.374A>G) in a patient with palmoplantar keratoderma (PPK) and congenital pachyonychia. Sanger sequencing and segregation analysis confirmed the variant detected in WES. For case 3, a patient with linear nevus comedonicus was found to have a somatic missense mutation in NEK9 (exon4:c.500T>C), which was only detected in the lesional DNA sample. Thus, WES shows great potential as a diagnostic tool for monogenic or oligogenic genodermatoses. Since omics is a technology-driven tool, we expect that reaching precision medicine is ever closer.