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

[junctional epidermolysis bullosa]

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 .To clarify the pathogenesis of JEB-lo .Two patients with JEB-lo , a brother and a sister , were examined using electron microscopy (EM ), immunofluorescence (IF ) antigen mapping and molecular analysis .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 (Col 17 ), and a broadened distribution of mAb staining against the ectodomain of Col 17 , laminin-332 and type VII collagen . Mutation analysis of COL 17 A 1 , encoding Col 17 , showed a compound heterozygosity for a novel mutation c .1992 _1995 delGGGT and the known mutation c .3908 G >A in both patients . The deletion c .1992 _1995 delGGGT results in a premature termination codon and mRNA decay , leaving the patients functionally hemizygous for the missense mutation c .3908 G >A (p .R 1303 Q ) in the noncollagenous 4 domain of Col 17 .JEB-lo is an autosomal recessive disorder caused by mutations in COL 17 A 1 , and subtle aberrations in EM and IF antigen mapping are clues to diagnosis .