Junctional epidermolysis bullosa of late onset explained by mutations in COL17A1.

ABSTRACT

BACKGROUND: Junctional epidermolysis bullosa of late onset (JEB-lo) is a rare disease characterized by blistering of primarily the hands and feet starting in childhood. The pathogenesis remains unclear. OBJECTIVES: To clarify the pathogenesis of JEB-lo. METHODS: Two patients with JEB-lo, a brother and a sister, were examined using electron microscopy (EM), immunofluorescence (IF) antigen mapping and molecular analysis. RESULTS: We found subtle changes in IF antigen mapping and EM. The most remarkable changes were loss of the apical-lateral staining of monoclonal antibodies (mAbs) against type XVII collagen (Col17), and a broadened distribution of mAb staining against the ectodomain of Col17, laminin-332 and type VII collagen. Mutation analysis of COL17A1, encoding Col17, showed a compound heterozygosity for a novel mutation c.1992_1995delGGGT and the known mutation c.3908G>A in both patients. The deletion c.1992_1995delGGGT results in a premature termination codon and mRNA decay, leaving the patients functionally hemizygous for the missense mutation c.3908G>A (p.R1303Q) in the noncollagenous 4 domain of Col17. CONCLUSIONS: JEB-lo is an autosomal recessive disorder caused by mutations in COL17A1, and subtle aberrations in EM and IF antigen mapping are clues to diagnosis.