ACOL7A1variant leading to in-frame skipping of exon 15 attenuates disease severity in recessive dystrophic epidermolysis bullosa

Funding sources: The work of C.H. is supported by Debra International, the Fritz Thyssen Foundation and the Else Kröner‐Fresenius Foundation. Conflicts of interest: none declared. Dear Editor, Dystrophic epidermolysis bullosa (EB) is a heritable skin fragility disorder, characterized by trauma‐induced blister formation and healing with scarring.1 Mutations in the collagen VII gene (COL7A1), which, by definition, disturb the functionality and/or the amount of this protein, result in a broad spectrum of dystrophic EB phenotypes.2 The severe generalized subtype is a devastating and lifespan‐limiting disorder marked by multisystem involvement and extensive blistering of skin and mucosal membranes, resolving with scarring and functional impairment. In the intermediate and localized dystrophic EB subtypes, blistering can be restricted to areas of maximal mechanical exposure, such as hands and feet. The clinical severity of dystrophic EB mainly depends on the nature and location of the COL7A1 mutations and on their consequences on mRNA and protein level. Phenotypic variation has been attributed to genetic modifiers, environmental factors, random events and interactions between any of these factors.3 So far, in single studies, variants in the gene for matrix metalloproteinase 1 and differences in the transforming growth factor‐β pathway have been documented as modifiers of dystrophic EB severity.4 5