Factors Beyond COL7A1 Mutations May Contribute to Dystrophic EB Forms, Study Suggests

A study from Spain has raised the possibility that the development of dystrophic epidermolysis bullosa (DEB) could be attributable to additional factors besides mutations in the COL7A1 gene. Researchers reached this conclusion after studying three unrelated patients with different forms of DEB who had two identical mutations in the COL7A1 gene.

The case report, titled “Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes,” was published in the journal Pediatric Dermatology.

DEB is one of the major forms of epidermolysis bullosa, characterized by blisters that often leave scars when they heal. It is thought to be caused by mutations in the COL7A1 gene, which encodes a type VII collagen that is a major component of adhesion between layers of skin.

These mutations lead to type VII collagen being morphologically altered, reduced in number, or completely absent, and to different variants of the disease. However, no clear correlation between specific COL7A1 mutations and the type of DEB has yet been established.

Spanish researchers examined the case of a 7-year-old girl whose disease changed as she grew older, from a mild form of DEB at 6 months to DEB pruriginosa (DEB-Pr) in the previous year. DEB-Pr is a rare subtype characterized by skin lesions associated with severe itching.

Two other patients — a 3-year-old boy and a 40-year-old man — had a less severe condition called Non-Hallopeau-Siemens.

All three patients were found to possess a novel mutation (c.7270C>T) that alters the gene sequence, and a previously identified mutation (c.6527insC) that leads to premature termination of protein synthesis. The latter is the most prevalent COL7A1 mutation causing recessive DEB in Spain.

Researchers observed a variable pattern of reduction or absence of collagen VII in the skin of these patients. What they had in common was the abnormal structure of the molecule.

The fact that identical mutations can result in different types of DEB suggests that “additional factors, genetic and environmental, may play a significant role in the pathogenesis [development] of this heterogeneous disease,” the team concluded.

“Clinical management of DEB is difficult and DEB-Pr is notoriously challenging to treat,” researchers wrote, adding that “further research is needed to unravel prognostic information and shape optimal management for our patients.”