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Scaffold abnormalities account for barrier abnormality in lamellar ichthyosis and loricrin keratoderma. Milder clinical phenotype in loricrin keratoderma correlates with compensatory cross-linking of other cornified envelope (CE) precursors. In contrast, CE is absent or defective throughout stratum corneum (SC) in transglutaminase 1-negative lamellar ichthyosis, correlating with a more severe phenotype.
