Both recessively and dominantly inherited forms of dystrophic epidermolysis bullosa have been shown to be linked to the collagen type VII gene, COL7A1.
We recently demonstrated strong genetic linkage between the type VII collagen gene (COL7A1) and both the dominant and recessive forms of dystrophic epidermolysis bullosa.
Dystrophic epidermolysis bullosa (DEB) is a rare hereditary skin disorder caused by mutations in COL7A1, encoding collagen type VII.1 Clinical manifestations of COL7A1 mutations range from generalized skin blistering to mild localized blistering or nail dystrophy.2 The investigation of the molecular basis of DEB has revealed more than 540 different mutations that cannot entirely explain phenotypic variations (HGMD Professional 2010.3, https://portal.biobase-international. com/hgmd/).
Dystrophic epidermolysis bullosa (DEB) pruriginosa (DEB-Pr) is a rare variant of DEB due to COL7A1 dominant and recessive mutations, which is characterized by severe itching and lichenoid or nodular prurigo-like lesions, mainly involving the extremities.
In screening the COL7A1 gene for mutations in individuals with DEB our data highlight that delineation of glycine substitutions in type VII collagen has important implications for genetic counselling.
We present three unrelated patients with two identical pathogenic compound heterozygous mutations in the COL7A1 gene that developed different clinical forms of dystrophic epidermolysis bullosa-epidermolysis bullosa pruriginosa and mild recessive non-Hallopeau-Siemens-raising the possibility of other genetic or environmental modifying factors responsible for the phenotype of the disease.
Naturally occurring exon skipping in COL7A1, translating collagen VII, suggests that skipping of exons containing disease-causing mutations may be feasible for the treatment of DEB.
Remarkably, identical mutations in COL7A1, which encodes an anchoring fibril protein present at the dermal-epidermal junction, can cause both DEB and EBP with either autosomal dominant or recessive inheritance.
Our results demonstrate that RTM28, which covers >60% of all mutations reported in DEB and is thus the longest RTM described so far for the repair of COL7A1, represents a promising candidate for therapeutic applications.
Functional impairment or complete loss of type VII collagen, caused by mutations within COL7A1, lead to the severe recessive form of the skin blistering disease dystrophic epidermolysis bullosa (RDEB).
Mutations in the gene COL7A1 encoding type VII collagen cause dystrophic epidermolysis bullosa, a clinically heterogeneous autosomal dominant or recessive blistering disorder of the skin and mucous membranes.