Background: Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous blistering disorder of the skin and mucous membranes. DEB is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. On the basis of the mode of inheritance and the clinical manifestations, DEB is classified into two major subtypes: one dominant (DDEB) and one recessive (RDEB).
Objective: We report, here, clinical, histological and genetic investigation of a large Tunisian family presenting with a wide range of clinical manifestations of DEB and a pedigree suggestive for a pseudodominant pattern of inheritance of a recessive mutation.
Methods: Indirect immunofluorescence (IF) with the antibody LH7:2 against collagen VII and electron microscopy (EM) analyses were performed. The members of the family were genotyped with five markers flanking COL7A1, and screening for the deleterious mutation by DHPLC and direct sequencing.
Results: The family presented four pretibial DEB patients and one generalized RDEB. Molecular investigation showed that all family members, unaffected and affected by the pretibial form, were heterozygous for the c.7178delT mutation, except for the member with the generalized form who was homozygous. IF showed that heterozygous individuals, independently of their clinical status, have a slightly reduced staining, and the homozygous individual with generalized DEB has markedly reduced staining at the dermal-epidermal junction.
Conclusion: These results are suggestive for an autosomal semidominant model of inheritance with incomplete penetrance and variable expression for the identified mutation. No genotype phenotype correlation was observed suggesting the existence of other genetic determinants influencing dermo-epidermal junction cohesion.