Haplotypic classification of dystrophic epidermolysis bullosa in Tunisian consanguineous families: implication for diagnosis

International audienceDystrophic epidermolysis bullosa (DEB) is a rare genodermatosis caused by mutations in the type VII collagen gene COL7A1. Clinical diagnosis of DEB should be confirmed by histopathological and electron microscopy analysis, which is not always accessible. We report here a genetic investigation of DEB consanguineous families in Tunisia. A total of 23 EB families were genotyped with 5 microsatellite markers overlapping the COL7A1 gene. Among these families, 19 presented with the dystrophic form of EB, 9 were diagnosed by histopathological examination, 2 had the simplex form, 1 had a junctional EB, and 1 was affected by an unclassified form of EB. The informativeness of the markers was studied and allowed us to select three markers for genetic testing of DEB in Tunisian families at risk. Haplotype analysis and homozygosity by descent suggest that all families classified clinically as having DEB and the patient who presented with an unclassified form of EB are likely linked to the COL7A1 gene, and showed evidence for exclusion for the simplex and junctional cases. For COL7A1 linked families, two main haplotypes were shared by eight families. For all the other cases, haplotypic heterogeneity was observed, thus suggesting a mutational heterogeneity among Tunisian DEB families. The genetic results matched with the ultrastructural analysis in all the DEB families and with the clinical examination in 94.7% of all studied DEB families. This study is to our knowledge the first genetic investigation of DEB in the Maghrebian population. We propose a selection of informative markers and show the importance of haplotype analysis as a relatively easy and cost and time effective method for carrier screening and prenatal diagnosis of DEB in consanguineous families at risk