Genetic basis of dominant dystrophic epidermolysis bullosa in tunisian families and co-occurrence of dominant and recessive mutations

Dystrophic epidermolysis bullosa (DEB) is a rare genodermatosis characterized by extensive fragility of the skin, which forms blisters and scars following a minimal friction or mechanical trauma.1 It is inherited as either autosomal recessive (RDEB) or dominant (DDEB) manner. DDEB is characterized by a wide range of clinical heterogeneity. Indeed, the blistering tendency can be relatively mild and limited to areas of considerable trauma, as in the DDEB-pretibial (DDEB-pt), or be more generalized, as in the DDEB-generalized (DDEBgen). 2 A peculiar form of DDEB-gen presents with albopapuloid lesions. DDEB is usually caused by missense mutations in the COL7A1 gene

Genetic basis of dominant dystrophic epidermolysis bullosa in tunisian families and co-occurrence of dominant and recessive mutations

Dystrophic epidermolysis bullosa (DEB) is a rare genodermatosis characterized by extensive fragility of the skin, which forms blisters and scars following a minimal friction or mechanical trauma.1 It is inherited as either autosomal recessive (RDEB) or dominant (DDEB) manner. DDEB is characterized by a wide range of clinical heterogeneity. Indeed, the blistering tendency can be relatively mild and limited to areas of considerable trauma, as in the DDEB-pretibial (DDEB-pt), or be more generalized, as in the DDEB-generalized (DDEBgen). 2 A peculiar form of DDEB-gen presents with albopapuloid lesions. DDEB is usually caused by missense mutations in the COL7A1 gene

Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia

Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background