2 New Mutations Linked to Epidermolysis Bullosa Pruriginosa in Case Study

Two novel mutations in the COL7A1 gene have been linked to epidermolysis bullosa pruriginosa (EBP), which is characterized by severe itching of the skin, or pruritus, according to a case report.

The case study, “Epidermolysis Bullosa Pruriginosa associated with recessive homozygous mutations in COL7A1: Case Report of a Rare EB Genotype-Phenotype,” was published in the Journal of The European Academy of Dermatology and Venereology.

EBP is characterized by intense pruritus, blisters, and other skin lesions. Such symptoms usually appear in the second or third decade of life, often following a history of fragile skin and blistering during childhood.

The condition is caused by mutations in the COL7A1 gene that gives rise to type VII collagen protein, which is involved in the maintenance of skin structure. Yet, the relation between COL7A1 mutations and disease severity is poorly understood.

Most cases are associated with a variant in one of two COL7A1 gene copies — so-called autosomal dominant as having one mutated gene copy is sufficient to develop the disease. Evidence suggests that less than 15% of cases are caused by recessive mutations, meaning that both gene copies need to carry the mutation for the disease to manifest.

A team from Ireland and the U.K. described the case of a 44-year-old man who had multiple itching lesions on his shins for 10 years. As a child, he had been diagnosed with dystrophic EB. His condition improved with age and was absent during adolescence. The patient had a history of multiple sclerosis and immune thrombocytopenic purpura, a rare autoimmune disease that causes a drop in the levels of platelets, the cells that help stop bleeding.

He had no family history of skin fragility or nail dystrophy, which refers to distortion or discoloration of the nails. Clinical examination showed he had multiple violet nodules and plaques in the lower legs with intense milia (cysts). Also, the patient presented scarring in the elbows, knees, and knuckles, and dystrophy of toenails and fingernails.

A skin biopsy was consistent with dystrophic EB. Genetic tests revealed two heterozygous mutations in the COL7A1 gene — known as c.4341-1G>T and c.7521+1G>A. Both mutations corresponded to a change in a nucleotide, the building blocks of DNA, that was predicted to disrupt the normal processing of the COL7A1 gene to produce type VII collagen.

Although each mutation by itself could cause EB, the lack of clinical features in the patient’s family suggests the disease to be recessive, the team said.

Daily treatment with clobetasol 17‐propionate 0.05% ointment led to complete resolution of pruritus within four weeks. Treatment was then switched to tacrolimus monohydrate 0.1% ointment as maintenance therapy.

“We report a rare EB phenotype caused by a rarer recessive genotype. We highlight the importance of genetic testing to optimise genetic counselling for patients with EB,” the scientists wrote.