Junctional Epidermolysis Bullosa: Allelic Heterogeneity and Mutation Stratification for Precision Medicine

Junctional epidermolysis bullosa (JEB) is a hereditary blistering disease caused by reduced dermal-epidermal adhesion due to deficiencies of one of the proteins, laminin-332, type XVII collagen, integrin α6β4 or integrin α3. Significant progress has been achieved in the development of therapies for EB, such as bone-marrow transplantation, local or systemic injections with fibroblasts or mesenchymal stromal cells, readthrough of premature termination codons, or exon skipping. These were tailored in particular for dystrophic EB, which is caused by type VII collagen deficiency and have not yet reached broad clinical practice. Recently, pioneering combined gene and stem cell therapy was successful in treating one boy with junctional EB. Beside these exclusive approaches, no specific therapy to amend the major clinical features, skin and mucosal blistering and non-healing wounds is available to date. Here we extend the mutational spectrum of junctional EB, provide a stratification of COL17A1 mutations and discuss potential molecular therapeutic approaches

Read-Through for Nonsense Mutations in Type XVII Collagen-Deficient Junctional Epidermolysis Bullosa

The project is funded by E-Rare-3 Joint Translational Call 2017 (to CH, MR, and FLL) and Bundesministerium für Bildung und Forschung 01GM1805 (to CH). IC received a fellowship from the European Academy of Dermatology and Venereology. We thank Blanca Duarte for skin-equivalent grafting procedures. The funding sources for this study : ERA-NET E-RARE JTC 2017 (MutaEB) (CH, MR, and FLL), (Grant AC17/00054 [FLL]) cofunded with European Regional Development Funds, BMBF 01GM1805, EADV (IC