Collagen XVII and Its Role in Junctional Epidermolysis Bullosa

Abstract

Collagen XVII is a major structural component of the hemidesmosomes, highly specialised multiprotein complexes that mediate the anchorage of basal epithelial cells to the underlying basement membrane. It is a homotrimeric type II transmembrane protein consisting of three 180 kDa alpha-1 (XVII) chains. Each individual chain is encoded by the COL17A1 gene. Mutations in COL17A1 usually lead to loss of collagen XVII and a phenotype comprising congenital generalised blistering and other signs which develop with advancing age, such as skin atrophy and dyspigmentation, dystrophy and loss of nails and alopecia. Mucosal involvement is mild and may be oral, ocular, nasal and genitourinary. Teeth are always affected by amelogenesis imperfecta, manifesting as enamel pits, and by increased incidence of caries. Milder skin fragility and variable degrees of nail and dental involvement are associated with COL17A1 mutations allowing residual protein expression. Molecular diagnosis relies on immunofluorescence mapping which indicates junctional cleavage of the skin, and loss or attenuated signal for collagen XVII, and on mutation analysis. Predictions on the consequences of the mutations and genotype-phenotype correlations require RNA and protein studies. Precise molecular diagnosis and recent developments in understanding the molecular genetics and biology of collagen XVII open perspectives for novel therapeutic approaches..