Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with <i>CERS3</i> mutations

The stratum corneum (SC) of the epidermis acts as a skin permeability barrier, and abnormalities in SC formation lead to several disorders. Lipids, especially epidermis-specific ceramide classes ?-O-acylceramides (acylceramides) protein-bound ceramides, are essential for barrier formation. Ceramide synthase 3 (CERS3) is involved synthesis acylceramides CERS3 mutations cause autosomal recessive congenital ichthyosis. In present study, we measured activity performed comprehensive profiling an ichthyosis patient with compound heterozygous mutations: nonsense mutation p.Arg75* missense p.Arg229His. p.Arg229His mutant proteins was reduced 4% 56%, respectively, wild-type protein. patient’s SC, acylceramide levels were greatly reduced, but ceramides remained almost unchanged. Non-acylated also affected patient; particular, composed sphingosine non-hydroxy or ?-hydroxy fatty acid substantially higher than healthy controls. These results suggest that reduction alone leads Although synthesized from acylceramides, not necessarily correlated.