Premium
Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with CERS3 mutations
Author(s) -
Yamamoto Moe,
Sassa Takayuki,
Kyono Yuki,
Uemura Hiroyasu,
Kugo Masaaki,
Hayashi Hideki,
Imai Yasutomo,
Yamanishi Kiyofumi,
Kihara Akio
Publication year - 2021
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.15725
Subject(s) - ceramide , stratum corneum , sphingolipid , ichthyosis , sphingosine , missense mutation , congenital ichthyosis , ceramide synthase , mutant , corneocyte , chemistry , biology , biochemistry , microbiology and biotechnology , mutation , genetics , gene , receptor , apoptosis
Abstract The stratum corneum (SC) of the epidermis acts as a skin permeability barrier, and abnormalities in SC formation lead to several skin disorders. Lipids, especially the epidermis‐specific ceramide classes ω‐ O ‐acylceramides (acylceramides) and protein‐bound ceramides, are essential for skin barrier formation. Ceramide synthase 3 (CERS3) is involved in the synthesis of acylceramides and protein‐bound ceramides, and CERS3 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 CERS3 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‐type protein. In the patient’s SC, acylceramide levels were greatly reduced, but the levels of protein‐bound ceramides remained almost unchanged. Non‐acylated ceramide levels were also affected in the patient; in particular, the levels of ceramides composed of sphingosine and non‐hydroxy or α‐hydroxy fatty acid were substantially higher than in healthy controls. These results suggest that a reduction in acylceramide levels alone leads to ichthyosis. Although protein‐bound ceramides are synthesized from acylceramides, levels of acylceramides and protein‐bound ceramides are not necessarily correlated.