THE 97 KDA LINEAR IGA BULLOUS DERMATOSIS ANTIGEN IS NOT EXPRESSED IN A PATIENT WITH GENERALIZED ATROPHIC BENIGN EPIDERMOLYSIS-BULLOSA WITH A NOVEL HOMOZYGOUS G258X MUTATION IN COL17A1

The nature and expression pattern of the 97 kDa linear IgA bullous der matosis antigen (LAD-1) and its role in epidermolysis bullosa have not been fully elucidated. In this study, we examined the expression of L AD-1 in the skin specimens of 70 patients with the various subtypes of epidermolysis bullosa, including simplex (n = 23), junctional (n = 15 ), and dystrophic variants (n = 32), For immunolabeling, we used two r ecently developed monoclonal antibodies to LAD-1 whose epitopes were u ltrastructurally localized in the lamina lucida between NC16A and carb oxyterminal domains of BPAG2, as well as autoantibodies against: LAD-1 from the sera of two patients with linear IgA dermatosis, Among the 7 0 patients, only one patient with generalized atrophic benign epidermo lysis bullosa failed to demonstrate LAD-1 expression. Although other m ajor basement membrane components, including laminin 5, BPAG1, plectin , alpha 6 and beta 4 integrins, as well as type IV and type VII collag ens were normally expressed, BPAG2/type XVII collagen was absent from the skin of this patient. Mutation analysis on COL17A1 using polymeras e chain reaction amplification, heteroduplex scanning, and direct nucl eotide sequencing revealed that this patient was homozygous for a nove l nonsense mutation G258X in exon 11, and her parents were heterozygou s carriers for this mutation, This is the first mutation located in th e intracellular domain of BPAG2, and resides 817 bp upstream from the N-terminal amino acid sequence of LAD-1, These findings indicate that the absent expression of LAD-1 is observed in a BPAG2-deficient genera lized atrophic benign epidermolysis bullosa patient with mutations in both alleles of COL17A1, and not in other epidermolysis bullosa subtyp es. These findings also support the notion that LAD-1 is a degradation product of BPAG2.