Restoration of open reading frame resulting from skipping of an exon with an internal deletion in the COL7A1 gene

Restoration of open reading frame resulting from exon skipping has been documented as a mechanism of rescuing an mRNA transcript containing mutations. In this study, we describe a mutation in a family with dystrophic epidermolysis bullosa consisting of a 16-bp deletion within exon 87 of the type VII collagen gene (COL7A1) and predicted to lead to a frameshift and downstream premature termination codon. Unexpectedly, mRNA analysis revealed instead that the intraexonic deletion led to skipping of exon 87 and subsequent restoration of the open reading frame. The phenotypes and patterns of inheritance observed in this family arise from three different mutations, all of which affect RNA processing. Restoration of open reading frame by exon skipping represents a previously undescribed mechanism of action of intraexonic deletion mutations.