Antenatal diagnosis of recessive dystrophic epidermolysis bullosa: collagenase expression in cultured fibroblasts as a biochemical marker.

We performed fetoscopy and skin biopsy on a 19-week fetus at risk for recessive dystrophic epidermolysis bullosa (RDEB). Ultrastructural analysis of the tissue revealed dermolytic blister formation in the skin characteristic of the disease. To develop a biochemical test for use in antenatal diagnosis of RDEB, we established skin fibroblast cultures from the 20-week aborted fetus. The collagenase production by fetal RDEB fibroblast cultures was greater than seen in normal fetal fibroblast cultures. The concentration in culture medium from fetal RDEB cultures was 5.42 +/- 0.74 micrograms/ml (mean +/- SE) compared with 2.24 +/- 1.11 micrograms/ml in normal adult control cultures and 2.05 +/- 0.61 micrograms/ml in cultures from patients with other genetic forms of epidermolysis bullosa (p less than 0.025). In contrast, the concentration of collagenase in the fetal RDEB culture medium was not different from that seen in cell cultures from known patients with RDEB (5.34 +/- 1.12 micrograms/ml). Collagenase activity of the fetal RDEB medium was also increased approximately 3.5-fold. These data indicate that enhanced expression of collagenase by fetal RDEB skin fibroblasts can serve as a biochemical adjunct, and possibly an alternative, to morphologic examination of tissue for antenatal diagnosis.