Compound heterozygosity of the novel 186C>T mutation in the COL7A1 promoter and the recurrent c.497insA mutation leads to generalized dystrophic epidermolysis bullosa

Dystrophic epidermolysis bullosa (DEB) is a rare genodermatosis characterised by trauma-induced blister formation beneath the lamina densa in the papillary dermis. Other clinical findings include atrophic scarring, milia formation, fusion of digits, nail dystrophy and contractures. DEB comprises 13 variants with different mucocutaneous involvement. All variants result from either dominant or recessive (RDEB) mutations in the COL7A1 gene, which encodes type VII collagen (COLVII). COLVII is the major component of anchoring fibrils (AFs), which ensure dermal–epidermal adhesion. To date, 636 distinct mutations throughout this gene have been reported, and general genotype–phenotype correlations have been defined. Here, we report an Italian RDEB patient (generalised subtype) with a mild phenotype who is compound heterozygous for a novel -186C>T mutation in the COL7A1 promoter and the recurrent c.497insA mutation. The -186C>T mutation is the second in the COL7A1 promoter reported to date; the first was the -187C>T identified in heterozygosity in a patient with severe generalised RDEB phenotype. Both mutations are in the same consensus sequence for the Sp1 transcription factor, but they have different effects on COL7A1 transcription, therefore producing different clinical phenotypes. This work underlines that COL7A1 promoter mutation are very rare, but this region should be investigated in RDEB patients with only a heterozygous mutation identified.