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Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of mechanobullous diseases characterized by non-scarring blisters and erosions on the skin and mucous membranes upon mechanical trauma. The simplex form (EBS) is characterized by recurrent blister formation within the basal layer of the epidermis. It most often results from dominant mutations in the genes coding for keratin (K) 5 or 14 proteins (KRT5 and KRT14). A disruptive mutation in KRT5 or KRT14 will not only structurally impair the cytoskeleton, but it will also activate a cascade of biochemical mechanisms contributing to EBS. Skin lesions are painful and disfiguring and have a significant impact on life quality. Several gene expression studies were accomplished on mouse model and human keratinocytes to define the gene expression signature of EBS. Several key genes associated with EBS were identified as specific immunological mediators, keratins, and cell junction components. These data deepened the understanding of the EBS pathophysiology and revealed important functional biological processes, particularly inflammation. This review emphasizes the three EBS subtypes caused by dominant mutations on either KRT5 or KRT14 (localized, intermediate, and severe). It aims to summarize current knowledge about the EBS expression profiling pattern and predicted molecular mechanisms involved and to outline progress in therapy. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa simplex (EBS) is a rare skin disease usually inherited in an autosomal dominant pattern. EBS is resulting from mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes encoding the keratins 5 and 14 proteins expressed in the keratinocytes of the basal layer of the epidermis. To date, seven pathogenic mutations have been reported to be responsible for EBS in the Canadian population from the province of Quebec: p.Pro25Leu, p.Leu150Pro, p.Met327Thr and p.Arg559X in KRT5; p.Arg125Ser, p.Ile377Thr and p.Ile412Phe in KRT14. Here, we present a novel French‐Canadian patient diagnosed with EBS confined to the soles but presenting a severe complication form including blisters, hyperkeratosis, skin erosions and toenail abnormalities. Mutation screening was performed by direct sequencing of the entire coding regions of KRT5 and KRT14 genes and revealed the previously reported missense heterozygous mutation c. 1130T > C in KRT14 (p.Ile377Thr). Furthermore, this patient is carrying a second mutation in KRT5, c.413G > A (p.Gly138Glu), which has been linked to an increased risk of basal cell carcinoma in the literature. We suspect an impact of the p.Gly138Glu variant on the EBS phenotype severity of the studied patient. The pathogenicity and consequences of both genetic variations were simulated by in silico tools. [ABSTRACT FROM AUTHOR]

(1) Background: The atopic march is defined by the increased prevalence of allergic diseases after atopic dermatitis onset. In fact, atopic dermatitis is believed to play an important role in allergen sensitization via the damaged skin barrier, leading to allergic diseases such as allergic asthma and allergic rhinitis. The eosinophil, a pro-inflammatory cell that contributes to epithelial damage, is one of the various cells recruited in the inflammatory reactions characterizing these diseases. Few studies were conducted on the transcriptome of this cell type and even less on their specific microRNA (miRNA) profile, which could modulate pathogenesis of allergic diseases and clinical manifestations post-transcriptionally. Actually, their implication in allergic diseases is not fully understood, but they are believed to play a role in inflammation-related patterns and epithelial cell proliferation. (2) Methods: Next-generation sequencing was performed on RNA samples from eosinophils of individuals with atopic dermatitis, atopy, allergic rhinitis and asthma to obtain differential counts of primary miRNA (pri-miRNA); these were also analyzed for asthma-related phenotypes such as forced expiratory volume in one second (FEV 1 ), immunoglobulin E (IgE) and provocative concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 s (PC 20 ) levels, as well as FEV 1 to forced vital capacity (FEV 1 /FVC) ratio. (3) Results: Eighteen miRNAs from eosinophils were identified to be significantly different between affected individuals and unaffected ones. Based on counts from these miRNAs, individuals were then clustered into groups using Ward's method on Euclidian distances. Groups were found to be explained by asthma diagnosis, familial history of respiratory diseases and allergic rhinitis as well as neutrophil counts. (4) Conclusions: The 18 differential miRNA counts for the studying phenotypes allow a better understanding of the epigenetic mechanisms underlying the development of the allergic diseases included in the atopic march.