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Lipids, especially the epidermis\u2010specific ceramide classes \u03c9\u2010<jats:italic>O<\/jats:italic>\u2010acylceramides (acylceramides) and protein\u2010bound ceramides, are essential for skin barrier formation. Ceramide synthase 3 (CERS3) is involved in the synthesis of acylceramides and protein\u2010bound ceramides, and <jats:italic>CERS3<\/jats:italic> mutations cause autosomal recessive congenital ichthyosis. In the present study, we measured ceramide synthase activity and performed comprehensive SC ceramide profiling in an ichthyosis patient with compound heterozygous <jats:italic>CERS3<\/jats:italic> mutations: nonsense mutation p.Arg75* and missense mutation p.Arg229His. The activity of p.Arg75* and p.Arg229His mutant CERS3 proteins was reduced to 4% and 56%, respectively, of the wild\u2010type protein. In the patient\u2019s SC, acylceramide levels were greatly reduced, but the levels of protein\u2010bound ceramides remained almost unchanged. Non\u2010acylated ceramide levels were also affected in the patient; in particular, the levels of ceramides composed of sphingosine and non\u2010hydroxy or \u03b1\u2010hydroxy fatty acid were substantially higher than in healthy controls. These results suggest that a reduction in acylceramide levels alone leads to ichthyosis. Although protein\u2010bound ceramides are synthesized from acylceramides, levels of acylceramides and protein\u2010bound ceramides are not necessarily correlated.<\/jats:p>","DOI":"10.1111\/1346-8138.15725","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T21:43:21Z","timestamp":1611611001000},"page":"447-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with <i>CERS3<\/i> mutations"],"prefix":"10.1111","volume":"48","author":[{"given":"Moe","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry Faculty of Pharmaceutical Sciences Hokkaido University Sapporo 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