RECENT INSIGHTS INTO THE MOLECULAR-BASES OF HEREDITARY EPIDERMOLYSIS-BULLOSA

Hereditary epidermolysis bullosa (EB) are clinically heterogeneous disorders characterized by blistering and erosions of the epidermis in response to trauma. The molecular basis underlying the main forms of these diseases have been recently brought to light. The simplex types (EBS), characterized by blister formation within the epidermis at the level of basal keratinocytes, have been associated with specific mutations of keratins 5 and 14 leading to an impaired assembly of tonofilaments and fragility of keratinocytes. The dystrophic EB (DEB), where cleavage occurs within the upper dermis at the level of anchoring fibrils, have been genetically linked to the type VII collagen locus, with no evidence for genetic heterogeneity thus far. This progress has been made possible by the identification of a polymorphism within the recently cloned human collagen VII gene. In junctional EB (JEB), characterized by dermal-epidermal splitting occurring within the lamina lucida, the causative defect appears related to the expression of a laminin-like protein named nicein, localized to anchoring filaments of the hemidesmosomes. Molecular cloning of the nicein genes is employed to identify putative mutations underlying the different forms of this affection. The application of molecular genetic to study inherited disorders of the skin is likely to lead soon to new classifications of cutaneous diseases, a prerequisite of perfecting any future therapeutic approach.