A Case of Pretibial Epidermolysis Bullosa with Novel Mutations of the COL7A1 Gene

Abstract

Dear Editor: Pretibial epidermolysis bullosa (PEB) was first described by Kuske in 19461. The author reported two cases of PEB with recurrent blisters in a middle-aged man and his son. PEB is a rare subtype of dominant dystrophic epidermolysis bullosa (DDEB). Symptoms of DDEB usually appear in infancy, and severe blistering can be life-threatening. On the other hand, PEB is characterized by mild blistering, erosions, and milia localized to the shins. The age of onset is variable, and some patients do not develop signs and symptoms until adulthood. In previous studies, nine patients with mutations in the COL7A1 gene have been reported2 3 4 5. Herein, we report a case of late-onset PEB and new mutations in the COL7A1 gene. An 86-year-old Japanese male presented with a 1-month history of recurrent blisters on the shins. Several erythema, tense blisters, erosions, and scars after healing were present on his shins (Fig. 1A, B). All of his toenails were dystrophic (Fig. 1C). His fingernails, teeth, and hair were not involved. Toenail dystrophy had persisted from his childhood, and his father also had the condition. Blood investigations, including a complete blood picture, liver and renal functions, antinuclear antibody, anti-BP180 antibody, and immunoglobulin (Ig) patterns, reported normal results. A skin biopsy showed a subepidermal bulla with poor inflammatory cell infiltration. The roof of the blister was intact. Mild infiltration of lymphocytes, neutrophils, and histiocytes was observed (Fig. 1D). At the epidermal side and the dermal side of the blister, direct immunofluorescence showed no deposition of IgG, IgM, IgA, and C3. Immunohistochemistry using an anti-collagen type VII monoclonal antibody revealed that staining was less intense at the basement membrane (Fig. 1E, F). Total RNA was extracted from peripheral blood, and cDNA was synthesized. Direct sequencing was performed to detect mutations in the COL7A1 gene. We identified two novel glycine substitution mutations, namely c.5264G>T (p.Gly1755Val) and c.5345G>C (p.Gly1782Ala), in exons 59 and exon 61, respectively. Both mutations have not been previously reported (Fig. 1G). After starting treatment with topical corticosteroid and vitamin D3 ointments, no blisters appeared. Milia occurred after lesions improved with topical benzoyl peroxide. In the nine cases previously reported, the age of onset of blisters and erosions on the shins ranged from 1 month to 52 years. Here, we present the oldest age of onset of blisters and erosions on the shins. Seven of the nine previously reported cases involved toenail dystrophy (Fig. 1H)2 3 4 5. This case also involved toenail dystrophy that started in childhood. Toenail dystrophy beginning in childhood may be a clue for PEB diagnosis. We report of two novel glycine substitution mutations in COL7A1 gene, c.5264G>T (p.Gly1755Val) and c.5345G>C (p.Gly1782Ala) in exons 59 and 61, respectively, that occurred in late-onset PEB. It is possible that the both mutations are on the same father-derived allele, but have relatively low impact on the anchoring fibril formation to generate mild phenotype. Another possibility is that one mutation is the father-derived dominant mutation and another mutation might be a silent glycine substitution mutation from his mother.