EBS is caused by mutations in the KRT14 gene.
More than 60 mutations in the KRT14 gene have been identified in people with EBS. Most of the mutation alters single protein building blocks — amino acids — used to make ‘keratin 14’.
The most severe form of EBS — the Dowling-Meara type — usually results from mutations in regions of the KRT14 gene which are essential for the normal assembly of keratin intermediate filaments.
Milder forms of the disorder — the Weber-Cockayne and Koebner types — are often caused by mutations in less critical regions.
The mutations in the KRT14 gene change the structure and function of ‘keratin 14’, preventing it from working effectively with ‘keratin 5’ and interfering with the assembly of the keratin intermediate filament network. A disruption in this network makes ‘keratinocytes’ fragile and prone to rupture. Minor trauma to the skin such as rubbing or scratching can cause these cells to break down, resulting in the formation of painful, fluid-filled blisters.