Tags

Type your tag names separated by a space and hit enter

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency.
J Lipid Res. 2018 12; 59(12):2413-2420.JL

Abstract

Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.

Authors+Show Affiliations

Department of Dermatology Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan takeichi@med.nagoya-u.ac.jp makiyama@med.nagoya-u.ac.jp.Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya 466-8550, Japan. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.Biological Science Research Laboratories Kao Corporation, Haga, Tochigi 321-3497, Japan.Department of Pediatrics Kumamoto University, Kumamoto 860-8556, Japan.Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.Department of Dermatology Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.Analytical Science Research Laboratories, Kao Corporation, Haga, Tochigi 321-3497, Japan.Department of Pediatrics Kumamoto University, Kumamoto 860-8556, Japan.Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.Department of Dermatology Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.Biological Science Research Laboratories Kao Corporation, Haga, Tochigi 321-3497, Japan.Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.Department of Dermatology Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan takeichi@med.nagoya-u.ac.jp makiyama@med.nagoya-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30348640

Citation

Takeichi, Takuya, et al. "Reduction of Stratum Corneum Ceramides in Neu-Laxova Syndrome Caused By Phosphoglycerate Dehydrogenase Deficiency." Journal of Lipid Research, vol. 59, no. 12, 2018, pp. 2413-2420.
Takeichi T, Okuno Y, Kawamoto A, et al. Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. J Lipid Res. 2018;59(12):2413-2420.
Takeichi, T., Okuno, Y., Kawamoto, A., Inoue, T., Nagamoto, E., Murase, C., Shimizu, E., Tanaka, K., Kageshita, Y., Fukushima, S., Kono, M., Ishikawa, J., Ihn, H., Takahashi, Y., & Akiyama, M. (2018). Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. Journal of Lipid Research, 59(12), 2413-2420. https://doi.org/10.1194/jlr.P087536
Takeichi T, et al. Reduction of Stratum Corneum Ceramides in Neu-Laxova Syndrome Caused By Phosphoglycerate Dehydrogenase Deficiency. J Lipid Res. 2018;59(12):2413-2420. PubMed PMID: 30348640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. AU - Takeichi,Takuya, AU - Okuno,Yusuke, AU - Kawamoto,Akane, AU - Inoue,Takeshi, AU - Nagamoto,Eiko, AU - Murase,Chiaki, AU - Shimizu,Eri, AU - Tanaka,Kenichi, AU - Kageshita,Yuichi, AU - Fukushima,Satoshi, AU - Kono,Michihiro, AU - Ishikawa,Junko, AU - Ihn,Hironobu, AU - Takahashi,Yoshiyuki, AU - Akiyama,Masashi, Y1 - 2018/10/22/ PY - 2018/06/06/received PY - 2018/10/21/revised PY - 2018/10/24/pubmed PY - 2019/9/3/medline PY - 2018/10/24/entrez KW - ceramide KW - skin barrier • ichthyosis • L-serine • sphingolipid SP - 2413 EP - 2420 JF - Journal of lipid research JO - J Lipid Res VL - 59 IS - 12 N2 - Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency. SN - 1539-7262 UR - https://www.unboundmedicine.com/medline/citation/30348640/Reduction_of_stratum_corneum_ceramides_in_Neu_Laxova_syndrome_caused_by_phosphoglycerate_dehydrogenase_deficiency_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2275(20)34166-3 DB - PRIME DP - Unbound Medicine ER -