SummaryBackground Fibroblast cell therapy can modify disease biology in recessive dystrophic epidermolysis bullosa (RDEB) although whether it improves wound healing is not clear. Objective To assess the effects of injecting of allogeneic fibroblasts into the margins of chronic erosions in individuals with RDEB in a prospective, double-blind, randomized, vehicle-controlled phase II trial. Methods Erosions were randomized 1 : 1, to either a single treatment of 5 9 10
Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4×10(-5); odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.
Desmosomes are intercellular junctions that contribute to cell-cell adhesion, signalling, development and differentiation in various tissues, including the skin. Composed of a network of transmembranous and intracellular plaque proteins, pathogenic autosomal dominant or recessive mutations have been reported in 10 different desmosomal genes, resulting in a spectrum of phenotypes variably affecting skin, hair and heart. This review summarizes the molecular pathology and phenotypes that predominantly affect the skin/hair. Recent desmosomal genodermatoses described include lethal congenital epidermolysis bullosa (plakoglobin), cardiomyopathy with alopecia and palmoplantar keratoderma (plakoglobin), hypotrichosis with scalp vesicles (desmocollin 3), and generalized peeling skin disease (corneodesmosin). Understanding the range of clinical phenotypes in combination with knowledge of the inherent desmosome gene mutation(s) is helpful in managing and counselling patients, as well as providing insight into the biological function of specific components of desmosomes in skin and other tissues.
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