ABSTRACT Collagen XVII has been identified as having a role in inherited junctional epidermolysis bullosa non-Herlitz (JEB-other, MIM #226650). The role of collagen XVII in both autoimmune and genetic blistering disorders demonstrates its relevance to dermal-epidermal adhesion. Collagen XVII is a major structural component of the hemidesmosome (HD), a highly specialized multiprotein complex that mediates the anchorage of basal epithelial cells to the underlying basement membrane in stratified, pseudostratified, and transitional epithelia. This article examines the genetic and pathological features of collagen XVII.
Article: The Genetics of Skin Fragility.[Show abstract] [Hide abstract]
ABSTRACT: Genetic skin fragility manifests with diminished resistance of the skin and mucous membranes to external mechanical forces and with skin blistering, erosions, and painful wounds as clinical features. Skin fragility disorders, collectively called epidermolysis bullosa, are caused by mutations in 18 distinct genes that encode proteins involved in epidermal integrity and dermal-epidermal adhesion. The genetic spectrum, along with environmental and genetic modifiers, creates a large number of clinical phenotypes, spanning from minor localized lesions to severe generalized blistering, secondary skin cancer, or early demise resulting from extensive loss of the epidermis. Laboratory investigations of skin fragility have greatly augmented our understanding of genotype-phenotype correlations in epidermolysis bullosa and have also advanced skin biology in general. Current translational research concentrates on the development of biologically valid treatments with therapeutic genes, cells, proteins, or small-molecule compounds in preclinical settings or human pilot trials. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 15 is September 01, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.Annual Review of Genomics and Human Genetics 09/2013; DOI:10.1146/annurev-genom-090413-025540 · 9.13 Impact Factor
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ABSTRACT: Cellulitis is responsible for over 400,000 bed days per year in the English National Health Service (NHS) at the cost of £96 million. An audit following transfer of care of lower limb cellulitis managed in secondary care from general physicians to dermatologists. Review of patient details and work diaries from the first 40 months of implementation of the new model of care. Of 635 patients referred with lower limb cellulitis 33% had other diagnoses which did not require admission. Four hundred and seven of 425 patients with cellulitis were managed entirely as outpatients, many at home. Twenty-eight per cent of patients with cellulitis had an underlying skin disease identified and treated, which is likely to have reduced the risk of recurrent cellulitis, leg ulceration and lymphoedema. Only 18 of 635 patients referred with lower limb cellulitis required hospital admission for conventional treatment. This new way of managing suspected lower limb cellulitis offered substantial savings for the NHS, and benefits of early and accurate diagnosis with correct home treatment for patients.British Journal of Dermatology 06/2011; 164(6):1326-8. DOI:10.1111/j.1365-2133.2011.10275.x · 4.10 Impact Factor
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ABSTRACT: Junctional epidermolysis bullosa of late onset (JEB-lo) is a rare disease characterized by blistering of primarily the hands and feet starting in childhood. The pathogenesis remains unclear. To clarify the pathogenesis of JEB-lo. Two patients with JEB-lo, a brother and a sister, were examined using electron microscopy (EM), immunofluorescence (IF) antigen mapping and molecular analysis. We found subtle changes in IF antigen mapping and EM. The most remarkable changes were loss of the apical-lateral staining of monoclonal antibodies (mAbs) against type XVII collagen (Col17), and a broadened distribution of mAb staining against the ectodomain of Col17, laminin-332 and type VII collagen. Mutation analysis of COL17A1, encoding Col17, showed a compound heterozygosity for a novel mutation c.1992_1995delGGGT and the known mutation c.3908G>A in both patients. The deletion c.1992_1995delGGGT results in a premature termination codon and mRNA decay, leaving the patients functionally hemizygous for the missense mutation c.3908G>A (p.R1303Q) in the noncollagenous 4 domain of Col17. JEB-lo is an autosomal recessive disorder caused by mutations in COL17A1, and subtle aberrations in EM and IF antigen mapping are clues to diagnosis.British Journal of Dermatology 04/2011; 164(6):1280-4. DOI:10.1111/j.1365-2133.2011.10359.x · 4.10 Impact Factor