GENETIC BASES OF EPIDERMOLYSIS-BULLOSA SIMPLEX AND EPIDERMOLYTIC HYPERKERATOSIS

Keratins are the major structural proteins of the epidermis. Analyzing keratin gene sequences, appreciating the switch in keratin gene expre ssion that takes place as epidermal cells commit to terminally differe ntiate, and elucidating how keratins assemble into 10-nm filaments hav e provided the foundation that has led to the discoveries of the genet ic bases of two major classes of human skin diseases. In this report, we review the cell biology and human genetics of these diseases, epide rmolysis bullosa simplex and epidermolytic hyperkeratosis. Both of the se diseases are epidermal disorders of keratin, typified by cell fragi lity as a consequence of defects in the mechanical strength of basal e pidermolysis bullosa simplex or suprabasal epidermolytic hyperkeratosi s cells.