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Autosomal dominant lamellar ichthyosis due to a missense variant in the gene NKPD1

The identification of monogenic causes for cornification disorders has enhanced our understanding of epidermal differentiation and skin barrier function. Autosomal dominant lamellar ichthyosis is a rare condition, and ASPRV1 was the only gene linked to autosomal dominant lamellar ichthyosis to date....

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Main Authors: Komlosi, Katalin (Author) , Glocker, Cristina (Author) , Hsu-Rehder, Hao-Hsiang (Author) , Alter, Svenja (Author) , Kopp, Julia (Author) , Hotz, Alrun (Author) , Zimmer, Andreas David (Author) , Haußer-Siller, Ingrid (Author) , Sandhoff, Roger (Author) , Oji, Vinzenz (Author) , Fischer, Judith (Author)
Format: Article (Journal)
Language:English
Published: December 2024
In: The journal of investigative dermatology
Year: 2024, Volume: 144, Issue: 12, Pages: 2754-2763,e1-e6
ISSN:1523-1747
DOI:10.1016/j.jid.2024.03.041
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jid.2024.03.041
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022202X24003038
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Author Notes:Katalin Komlosi, Cristina Glocker, Hao-Hsiang Hsu-Rehder, Svenja Alter, Julia Kopp, Alrun Hotz, Andreas David Zimmer, Ingrid Hausser, Roger Sandhoff, Vinzenz Oji and Judith Fischer
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Summary:The identification of monogenic causes for cornification disorders has enhanced our understanding of epidermal differentiation and skin barrier function. Autosomal dominant lamellar ichthyosis is a rare condition, and ASPRV1 was the only gene linked to autosomal dominant lamellar ichthyosis to date. We identified a heterozygous variant (ENST00000686631.1:c.1372G>T, p.[Val458Phe]) in the NKPD1 gene in 7 individuals from a 4-generation German pedigree with generalized lamellar ichthyosis by whole-exome sequencing. Segregation analysis confirmed its presence in affected individuals, resulting in a logarithm of the odds score of 3.31. NKPD1 encodes the NKPD1 protein, implicated in the plasma membrane; its role in human disease is as yet unknown. Skin histology showed moderate acanthosis and compact orthohyperkeratosis, and the ultrastructure differed clearly from that in ASPRV1-autosomal dominant lamellar ichthyosis. Although NKPD1 mRNA expression increased during keratinocyte differentiation, stratum corneum ceramides exhibited no significant changes. However, affected individuals showed an elevated ratio of protein-bound ceramides to omega-esterified ceramides. This highlights NKPD1's role in autosomal dominant lamellar ichthyosis, impacting ceramide metabolism and skin lipid barrier formation, as demonstrated through functional characterization.
Item Description:Online verfügbar 18 April 2024, Version des Artikels 20 November 2024
Gesehen am 02.07.2025
Physical Description:Online Resource
ISSN:1523-1747
DOI:10.1016/j.jid.2024.03.041

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