A homozygous nonsense mutation identified in COL7A1 in a family with autosomal recessive dystrophic epidermolysis bullosa.

Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of an inherited skin disorder. RDEB segregates both in an autosomal dominant as well as in an autosomal recessive pattern. It has been shown that both forms of dystrophic epidermolysis bullosa (DEB) are caused by mutations in the COL7A1 gene. In this study, we investigated a consanguineous four-generation family with two individuals displaying the RDEB phenotype. Both patients showed multiple skin erosions, atrophic scares, crusted scaling, and pseudosyndactyly. Whole exome sequencing (WES) was performed to identify the underlying genetic defect, revealing a homozygous nonsense mutation, c.409C>T (p.Arg137*) in COL7A1 in both patients. This variant was validated through Sanger sequencing and confirmed to segregate within the family. This report describes a recurrent nonsense mutation in COL7A1 that leads to a severe form of autosomal recessive dystrophic epidermolysis bullosa. Moreover, this study demonstrates that whole exome sequencing analysis is imperative in resolving clinically and genetically heterogeneous diseases like RDEB. Furthermore, this study expands the mutation spectrum of the COL7A1 gene in distinct populations.