Generalized dominant epidermolysis bullosa simplex: decreased activity of a gelatinolytic protease in cultured fibroblasts as a phenotypic marker.
To characterize biochemical traits associated with various forms of epidermolysis bullosa (EB), we used skin fibroblast cultures to measure a gelatin-specific neutral metalloprotease. Compared to normal cultures, levels of this gelatinase were 7-fold decreased in cell cultures from 3 patients from 3 kindreds with generalized dominant EB simplex of the Koebner type (DEBS-K) (p less than 0.001). The specificity of this trait was shown in several ways. The growth kinetics and total protein synthesis of the cells were unaltered. The activity of lactic dehydrogenase, a cytoplasmic enzyme, was also unaltered, indicating the integrity of the cells was not compromised. The decrease in gelatinase activity is specific for generalized DEBS-K, since cultures from recessive dystrophic EB, recessive junctional EB, dominant dystrophic EB, and a second genetic type of DEBS all fail to show this defect. However, since it has been suggested that DEBS-K and the localized form of DEBS, the Weber-Cockayne type (DEBS-WC), may represent allelic mutations of varying severity, we measured gelatinase activity in cell cultures of 13 patients of this type. The levels displayed a biphasic segregation in which 7 of 13 values were equal to, or greater than, the mean activity of control cells. Cultures from the remaining 6 patients were greater than 1 SD below the mean control value and approximated those seen in the generalized DEBS-K patients. These studies suggest that the decrease in gelatinolytic activity is a marker for DEBS-K and that DEBS-K and DEBS-WC may be closely related genetic disorders in which the defect in gelatinolytic protease represents a pleiotropic effect of the gene for DEBS or is genetically linked to the DEBS gene.
D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004820:Epidermolysis Bullosa / Q000201:enzymology* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D018093:Gelatinases; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010434:Pepsin A / Q000172:deficiency*; D010641:Phenotype
D010434:Pepsin A; D018093:Gelatinases