How Epidermolysis Bullosa Simplex [EBS] cause?

EBS is caused by mutations in the KRT5 gene.

More than 100 mutations in the KRT5 gene have been identified in people suffering with EBS. Most of the mutation alters single protein building blocks — amino acids — used to make ‘keratin 5’.

The most severe form of EBS — the Dowling-Meara type— usually caused by the mutations in the regions of keratin 5 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 of the protein.

Epidermis Bullosa Simplex with mottled pigmentation typically results from a particular KRT5 mutation. This mutation replaces the amino acid ‘proline’ with the amino acid ‘leucine’ at protein position 25 (expressed as Pro25Leu or P25L).

The mutations in the gene KRT5 change the structure and function of ‘keratin 5’, preventing it from working effectively with keratin 14 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 the formation of painful, fluid-filled blisters.