Absence of detectable alpha(6) integrin in pyloric atresia-junctional epidermolysis bullosa syndrome - Application for prenatal diagnosis in a family at risk for recurrence

Background and Design: The expression of basement membrane-related antigens was surveyed in 2 Japanese siblings who died of pyloric atresia-junctional epidermolysis bullosa syndrome in early infancy. Results: The skin specimens of both patients demonstrated complete absence of detectable alpha(6) integrin and markedly reduced amounts of beta(4) integrin. All the other subtypes of epidermolysis bullosa used as controls demonstrated normal intensity of expression of alpha(6) and beta(4) integrin. In contrast to the negative immunoreactivity of monoclonal antibody GB3 in gravis-Herlitz junctional epidermolysis bullosa (n=4), a bright linear pattern along the epidermal basement membrane was demonstrated in the skin of both siblings with pyloric atresia-junctional epidermolysis bullosa syndrome. Based on these data, a monoclonal antibody against alpha(6) integrin was successfully used as a prenatal diagnostic probe for a skin biopsy specimen from a fetus at risk for pyloric atresia-junctional epidermolysis bullosa syndrome in this family. Conclusion: The absence of detectable alpha(6) integrin, but not beta(4) integrin, in these cases raises the possibility that alpha(6) integrin or its ligands are responsible for the pyloric atresia-junctional epidermolysis bullosa syndrome phenotype seen in this family.