304 Sephardic Ancestry in Recessive Dystrophic Epidermolysis Bullosa Individuals Carrying the Prevalent c.6527insC Mutation

Epidermolysis Bullosa is a clinically and genetically heterogeneous rare blistering skin disorder. The most severe variant, Recessive Dystrophic Epidermolysis Bullosa (RDEB), is caused by loss-of-function mutations in the type VII collagen gene (COL7A1). The COL7A1 c.6527insC mutation in RDEB individuals is curiously prevalent and carries a unique genetic history. In this study, approximately 100 RDEB patients with the c.6527insC founder mutation from Spain, France, Argentina, Chile, Colombia, and the USA were investigated to identify common Sephardic ancestry. Nearly all individuals inherited a Sephardic segment that encompasses the c.6527insC mutation, despite mixed ancestry elsewhere in the genome and no knowledge of recent Sephardic ancestry. An age estimate analysis for the shared c.6527insC-containing haplotypes suggests an origin for the founding population dating around 500 years ago on the Iberian Peninsula. The identification of homogeneous RDEB subpopulations with common ancestral origins coupled with the development of promising gene and cell based regenerative therapies, will together facilitate the efficient implementation of new treatments for RDEB.