Heterogeneity of Severe Dystrophic Epidermolysis Bullosa: Overexpression of Collagen VII by Cutaneous Cells from a Patient with Mutilating Disease

Severe mutilating recessive dystrophic epidermolysis bullosa presents with extensive blistering, scarring, and pseudosyndactylies. The skin of most affected individuals lacks normal anchoring fibrils and contains no, or drastically reduced amounts of, collagen VII, the major fibril component. Here we present evidence for molecular heterogeneity of the mutations underlying this phenotype. A patient with severe mutilating disease, but with apparently normal anchoring fibrils and abundant collagen VII, was defined. Indirect immunofluorescence examination of the patient's skin exhibited a strong staining for collagen VII at the dermo-epidermal junction and at the roof of a natural blister, and immunoblotting of skin extracts revealed collagen VII of normal size. The patient's keratinocytes expressed two- to threefold increased amounts of collagen VII at the mRNA and protein level compared to controls. Synthesis of matrix metalloproteases by the patient's keratinocytes was comparable to normal cells, indicating that the overexpression of collagen VII did not affect the synthesis of these enzymes. We hypothesize that in this patient a mutation affecting interactions of the anchoring fibrils with other components of the basement membrane zone underlies the disease