Journal Article

DKFZ-2024-00835

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Autosomal dominant lamellar ichthyosis due to a missense mutation in the gene NKPD1.

Komlosi, K. ; Glocker, C. ; Hsu-Rehder, H.-H. ; Alter, S. ; Kopp, J. ; Hotz, A. ; Zimmer, A. D. ; Hausser-Siller, I. ; Sandhoff, R.DKFZ* ; Oji, V. ; Fischer, J.

2024
Elsevier Amsterdam

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Please use a persistent id in citations: doi:10.1016/j.jid.2024.03.041

Abstract: The identification of monogenic causes for cornification disorders has enhanced our understanding of epidermal differentiation and skin barrier function. Autosomal dominant lamellar ichthyosis (ADLI) is a rare condition, and ASPRV1 was the only gene linked to ADLI to date. We identified a heterozygous variant (ENST00000686631.1:c.1372G>T, p.(Val458Phe)) in the NKPD1 gene in seven individuals from a four-generation German pedigree with generalized lamellar ichthyosis by whole exome sequencing. Segregation analysis confirmed its presence in affected individuals, resulting in a LOD score of 3.31. NKPD1 encodes the NTPase KAP Family P-Loop Domain-Containing Protein 1, 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-ADLI. While 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 ADLI, impacting ceramide metabolism and skin lipid barrier formation, as demonstrated through functional characterization.

Keyword(s): Mendelian cornification disorders ; NKPD1 ; NTPases ; autosomal dominant lamellar ichthyosis ; non-syndromic autosomal dominant congenital ichthyosis ; whole exome sequencing

Note: Volume 144, Issue 12, December 2024, Pages 2754-2763.e6

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Contributing Institute(s):

1. Lipid-Pathobiochemie (A411)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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