Whole-exome sequencing in the clinical setting: Establishing a foothold for precision medicine in genodermatoses and other diseases

@#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.

Comparison of therapeutic effects of Artemisia sieberi 5% lotion with clotrimazole lotion in the treatment of pityriasis versicolor

Pityriasis versicolor [Tinea versicolor] is a common fungal disease and many topical and systemic drugs have been used for its treatment. But more or less the treatment results had been similar with high recurrence rates. The aim of this study was to compare the therapeutic effects of Artemisia sieberi 5% lotion with clotrimazole 1% lotion in the treatment of tinea versicolor. This was a double blind RCT study. 100 patients were divided into group 1 and group 2 by block randomization. Group 1 and group 2 comprised 51 and 49 patients respectively. Artemisia sieberi and clotrimazole lotions started for group 1 and group 2 accordingly and continued for 2 weeks. The patients were evaluated from clinical and laboratory points of view. The data collected were registered in check lists, introduced into SPSS win, and analyzed by means of independent T, x[2] and fisher's tests. In our study the cure rates at the end of the second week, from clinical point of view were 86.3% and 65.3% in group 1 and group 2 respectively [p=0.013], but from laboratory point of view the cure rates were 92.2% and 73.5% with a significant relationship [p<0.010]. Also 4 weeks after treatment [2 weeks after discontinuing the drugs] clinical improvement reached 86.3% an 59.2% in group 1 and group 2 respectively [p<0.01] which reveals an important relationship. In microscopic study, after 4 weeks the smears were negative in 96.1% and 65.3% of the patients of the group 1 and group 2 accordingly which disclosed a significant relationship [P<0.01]. The results of this study indicates that Artemisia sieberi lotion was more effective and had less recurrence rate than clotrimozole lotion in the treatment of pityriasis versicolor