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Novel heterozygous COL7A1 mutation in a patient with de-novo dominant dystrophic epidermolysis bullosa pruriginosa

DEB: dystrophic epidermolysis bullosa INTRODUCTION Dystrophic epidermolysis bullosa (DEB) is a blistering disease linked to a mutation in the COL7A1 gene, which encodes for type VII collagen, a major component of anchoring fibrils. DEB is due to an autosomal dominant or autosomal recessive mutation; the former is commonly associated with a milder form of the disease than the latter. The mutation can be sporadic or hereditary. The common cause of mutation in autosomal dominant DEB is often a heterozygous mutation, which results in an atypical conformation of the anchoring fibrils, thus preventing adhesion of the basement membrane to the dermis. Herein, we report a case with a novel mutation leading to autosomal dominant DEB.


INTRODUCTION
Dystrophic epidermolysis bullosa (DEB) is a blistering disease linked to a mutation in the COL7A1 gene, which encodes for type VII collagen, a major component of anchoring fibrils. 1,2 DEB is due to an autosomal dominant or autosomal recessive mutation; the former is commonly associated with a milder form of the disease than the latter. 2 The mutation can be sporadic or hereditary. The common cause of mutation in autosomal dominant DEB is often a heterozygous mutation, which results in an atypical conformation of the anchoring fibrils, thus preventing adhesion of the basement membrane to the dermis. [1][2][3][4][5][6] Herein, we report a case with a novel mutation leading to autosomal dominant DEB.

CASE REPORT
A 47-year-old woman presented to the dermatology clinic with a history of congenital toenail dystrophy and a recurrent blistering skin eruption, which had developed in adolescence. In the past, the patient was treated with topical, intralesional, and oral corticosteroids for presumptive atopic dermatitis, lichen planus, and dermatitis herpetiformis. Her symptoms temporarily resolved with the use of oral corticosteroids. The patient denied a family history of bullous disease in her parents or siblings. On physical examination, scattered, eroded papules and vesicles were observed on the back, buttocks, and abdomen with no involvement of the eyes, mouth, or genitalia (Fig 1, A-C ). Two punch biopsies of an intact vesicle on the lower back submitted to hematoxylin-eosin (H&E) staining and perilesional direct immunofluorescence (DIF) demonstrated subepidermal bullae with subtle dermal fibrosis and minimal perivascular inflammation with a negative DIF (Fig 2, A). A repeat perilesional punch biopsy for DIF of the lower abdomen was negative. Serum tissue transglutaminase antibody and indirect immunofluorescence with human salt-split skin and monkey esophagus were negative. Serum enzymelinked immunosorbent assays for BP180 and BP230 were negative. The patient had an upper endoscopy and colonoscopy with no findings suggestive of celiac disease. A complete metabolic panel was notable for transaminitis (aspartate transaminase, 120 IU/L; alanine aminotransferase, 239 IU/L) with negative hepatitis A, B, and C serology. Twentyfourehour urine porphyrins were within the normal limits. Both serum anti-mitochondrial antibody and smooth-muscle antibody were negative. The antinuclear antibody titer was 1:80. There was no evidence of iron overload, and the ceruloplasmin level was within the normal limits.
Subsequent genetic testing for epidermolysis bullosa using a next-generation sequencing-based panel (Prevention Genetics Epidermolysis Bullosa Panel V19.01) included covered the following genes:

DISCUSSION
Collagen VII is an important constituent of anchoring fibrils. 1 The single nucleotide polymorphism disrupts the consensus of the GT donor splice site; thus, the intron 74 is included in the protein product, albeit this has yet to be confirmed by a functional study. The patient's vesicles occur at sites of trauma, with reported involvement of the scalp, neck, back, buttocks, genitalia, and thighs with associated pruritus. The severity of her toenail dystrophy in childhood led to toenail removal, given significant discomfort while wearing shoes.
Given the patient's history, as well as the clinical and genetic findings, the patient may have a rare subtype of DEB, which is referred to as pruriginosa subtype. Since the diagnosis, the patient has been counseled regarding the disease and the risk of her children inheriting the mutation. She has also been recommended to apply non-adherent dressings to  her wounds and receive regular skin examinations due to an increased risk of developing skin cancer, particularly squamous cell carcinoma.