Jouni Uitto
DOI: 10.2340/00015555-0648

Epidermolysis bullosa, a group of blistering disorders, serves as the paradigm of the tremendous progress made in understanding the molecular genetics of heritable skin diseases. Mutations in 10 distinct genes have been disclosed in the classic forms of epidermolysis bullosa, and the level of expression of the mutated genes within the cutaneous basement membrane zone, the types and combinations of mutations and their consequences at the mRNA and protein levels, when placed in the context of the individual's genetic background and exposure to environmental trauma, all determine the subtype and the phenotypic severity in each case. The translational implications of mutation analysis include improved diagnosis and subclassification, refined genetic counseling of families at risk, and development of DNA-based pre natal and preimplantation genetic diagnosis. The prospects of molecular therapies for epidermolysis bullosa include further development of strategies for gene therapy, protein replacement therapy and cell-based therapies, including stem cell therapy and bone marrow transfer. Collectively, advances in the molecular genetics of heritable skin diseases clearly emphasize the value of basic research for improved diagnostics and patient care for genetic skin diseases.