The New England Journal of Medicine, 2012, Vol.366(16), pp.1508-1514
Integrin α 3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin α 3 gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. Three patients with homozygous mutations in the integrin α3 gene, a transmembrane integrin receptor subunit, were found to have disrupted basement-membrane structures causing congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. Epithelial–mesenchymal interactions are important in the development and tissue homeostasis of many multicompartment organs, such as the kidneys, lungs, and skin.1 Adhesion of epithelial cells to basement membranes provides the structural and functional integrity of the organs. Cues from the extracellular environment that are transduced to the cell and vice versa regulate adhesion, which is partially dependent on integrins.2 Mutations in integrin genes are associated with various human disorders, including epidermolysis bullosa with pyloric atresia, congenital muscular dystrophy, leukocyte adhesion deficiency, and Glanzmann's thrombasthenia.3,4 Integrin α3, which forms heterodimers with integrin β1, is widely expressed . . .