Background: Epidermolysis bullosa (EB) is a complex and heterogeneous dermatological disease. Four main types of EB have been described, each of them with distinct characteristics: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler EB (KEB). Each main type varies in its manifestations, severity, and genetic abnormality. Methods: We sought mutations in 19 genes known to cause EB and 10 genes associated with other dermatologic diseases in 35 Peruvian pediatric patients of a rich Amerindian genetic background. Whole exome sequencing and bioinformatics analysis was performed. Results: Thirty-four of 35 families revealed an EB mutation. Dystrophic EB was the most frequently diagnosed type, with 19 (56%) patients, followed by EBS (35%), JEB (6%), and KEB (3%). We found 37 mutations in seven genes; 27 (73%) were missense mutations; 22 (59%) were novel mutations. Five cases changed their initial diagnosis of EBS. Four were reclassified as DEB and one as JEB. Inspection into other non-EB genes revealed a variant, c.7130C>A, in the gene FLGR2, which was present in 31 of the 34 patients (91%). Conclusion: We were able to confirm and identify pathological mutations in 34 of 35 patients.

Background

Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear.

Objective

To better understand PC pathogenesis.

Methods

RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples.

Results

A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis.

Conclusion

Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.

Objective: To review the use of gentian violet in dermatology. Design: A comprehensive literature search on gentian violet in dermatology practice was performed through PubMed. Results: Gentian violet is effective in treating methicillin-resistant Staphylococcus aureus-colonized skin lesions; mean number of days for complete eradication was 9.1 days. Gentian violet is almost as effective as ketoconazole and more effective than nystatin in the treatment of oral thrush in AIDS patients. In an in vitro study on cutaneous T cell lymphoma cell lines, there was no difference between nitrogen mustard and gentian violet in stimulating apoptosis. When comparing gentian violet to silver sulfadiazine dressings in healing burn wounds, the gentian violet treatment group reported less pain, fewer febrile episodes, and decreased bacterial growth compared to control. In atopic dermatitis subjects, gentian violet decreased Staphylococcus aureus colonization and improved disease severity in lesional skin compared to non-lesional skin. Conclusion: Studies have investigated gentian violet's antibacterial, antifungal, antiviral, antiparasitic, anti-angiogenic, antitumor, and wound healing properties. Gentian violet is a low cost and well-tolerated topical agent with the potential for widespread applications in dermatology.

Widespread reversion of genetic disease is rare; however, such events are particularly evident in some skin disorders in which normal clones develop on a background of affected skin. We previously demonstrated that mutations in keratin 10 (KRT10) cause ichthyosis with confetti (IWC), a severe dominant disorder that is characterized by progressive development of hundreds of normal skin spots via revertant mosaicism. Here, we report on a clinical and histological IWC subtype in which affected subjects have red, scaly skin at birth, experience worsening palmoplantar keratoderma in childhood, and develop hundreds of normal skin spots, beginning at around 20 years of age, that increase in size and number over time. We identified a causal de novo mutation in keratin 1 (KRT1). Similar to IWC-causing KRT10 mutations, this mutation in KRT1 resulted in a C-terminal frameshift, replacing 22 C-terminal amino acids with an alternate 30-residue peptide. Mutant KRT1 caused partial collapse of the cytoplasmic intermediate filament network and mislocalized to the nucleus. As with KRT10 mutations causing IWC, reversion of KRT1 mutations occurred via mitotic recombination. Because reversion is not observed with other disease-causing keratin mutations, the results of this study implicate KRT1 and KRT10 C-terminal frameshift mutations in the high frequency of revertant mosaicism in IWC.