A founder COL17A1 splice site mutation leading to generalized atrophic benign epidermolysis bullosa in an extended inbred Palestinian family from Israel

Purpose: Generalized atrophic benign epidermolysis bullosa is a nonlethal form of junctional EB with an autosomal recessive inheritance. There is generalized cutaneous blister formation at sites of trauma, atrophic alopecia affecting scalp, eyelash and eyebrow, dystrophic nail changes, and tooth abnormalities. In this study, we have studied a five-generation Palestinian family affected with generalized atrophic benign epidermolysis bullosa. Methods: We have performed linkage analysis to genes that are mutated in generalized atrophic benign epidermolysis bullosa, followed by direct sequencing of patient genomic DNA. Results: We have shown that the disease is caused by a newly detected homozygous donor splice site mutation, IVS51+1G>A, in the type XVII collagen gene, COL17A1. Conclusion: The effect of a founder mutation introduced 3 to 4 generations before a disease appearance is demonstrated in this inbred family.