Epidermolysis bullosa (EB) is an inherited, heterogeneous group of rare genetic dermatoses characterized by mucocutaneous fragility and blister formation, inducible by minimal trauma (1). It has four major categories, based usually on the plane of cleavage within the skin and reflecting the underlying molecular abnormality: EB simplex, junctional EB, dystrophic EB and Kindler EB. The most feared of which — and also the leading cause of mortality — is squamous cell carcinoma (1). According to the layer of skin in which blistering occurs: epidermolysis bullosa simplex (intra epidermal), junctional epidermolysis bullosa (within the lamina lucida of the basement membrane), dystrophic epidermolysis bullosa (below the basement membrane), and Kindler epidermolysis bullosa (mixed skin cleavage pattern) (2). Pathogenic variants in at least 16 genes that encode proteins vital for the integrity and adhesion of skin layers have already been associated with different subtypes of epidermolysis bullosa (2). The deficiency and/or dysfunction of type VII collagen leads to subepidermal blistering immediately below the lamina densa, resulting in mucocutaneous fragility and disease complications such as intractable ulcers, extensive scarring, malnutrition, and malignancy (3). The disease is predominantly diagnosed by immunofluorescence mapping and/or transmission electron microscopy and subsequently subclassified into one of 14 subtypes (3). Dystrophic epidermolysis bullosa (DEB) is inherited in both an autosomal dominant DEB and autosomal recessive manner RDEB, both of these result from mutations in the type VII collagen gene (COL7A1). Dominant ystrophic epidermolysis bullosa predominantly involves glycine substitutions within the triple helix of COL7A1 although other missense mutations, deletions or splice-site mutations may underlie some cases (4). In recessive dystrophic epidermolysis bullosa, the mutations include nonsense, splice site, deletions or insertions, ‘silent’ glycine substitutions within the triple helix and non-glycine missense mutations within the triple helix or non-collagenous NC-2 domain (4). Procollagen VII is a homotrimer composed of three proa1 (VII) chains which are encoded by the 32 kbCOL7A1gene located on chromosome 3p21. The mRNA transcript of approximately 8.9 kb is translated into a proa1 (VII) polypeptide containing 2944 amino acids (4). RDEB is caused by mutations to the COL7A1 gene located on chromosome three. A lack of type VII collagen protein at the dermal-epidermal junction (DEJ) results in a loss of structural integrity of the skin. Patients with RDEB exhibit incurable, often fatal, skin blistering, and have an increased risk for aggressive squamous cell carcinoma (5).
