Clinically revertant skin in epidermolysis bullosa: A single-institute experience

Revertant mosaicism (RM) is a phenomenon in which inherited mutations are spontaneously corrected in somatic cells. Skin spots that look intact and may undergo RM (“clinically revertant skin”) are frequently observed in patients with epidermolysis bullosa (EB), a group of congenital skin fragility disorders resulting from mutations in the genes encoding basement membrane zone components. Here we characterize the clinically revertant skin of EB patients at a single institution. Four recessive dystrophic EB patients and one junctional EB patient were included in this study as having such skin spots, which did not show skin fragility by finger rubbing. Immunofluorescence studies confirmed RM in two cases by detecting the re-expression of defective proteins in the skin spots. However, in other cases, the expression at the protein level did not help verify RM, primarily due to generic leaked protein expression by missense/splice-site variants. At least one skin spot was confirmed to be RM by Cas9-guided long-read sequencing. These results highlight the difficulties of validating RM in clinically revertant skin in EB.