Autosomal recessive congenital ichthyosis caused by a pathogenic missense variant in CLDN1.

Autor: Mohamad J; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Samuelov L; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Assaf S; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Malki L; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Malovitski K; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Meijers O; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel., Adir N; Schulich Faculty of Chemistry, Technion, Haifa, Israel., Granot E; Shoham Medical Center, Pardes Hana, Israel., Pavlovsky M; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Sarig O; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel., Sprecher E; Division of Dermatology, Tel Aviv Medical Center, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2022 Oct; Vol. 188 (10), pp. 2879-2887. Date of Electronic Publication: 2022 Aug 03.
DOI: 10.1002/ajmg.a.62924
Abstrakt: Autosomal recessive congenital ichthyosis (ARCI) refers to a large and genetically heterogenous group of non-syndromic disorders of cornification featuring diffuse scaling. Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome is a rare autosomal recessive syndromic form of ichthyosis. The disease usually results from premature termination codon-causing pathogenic variants in CLDN1 encoding CLAUDIN-1 (CLDN1). We used whole exome sequencing (WES), Sanger sequencing, 3D protein modeling, Western blotting, and immunofluorescence confocal microscopy to delineate the genetic basis of ichthyosis in two siblings with ichthyosis but no other ectodermal abnormalities. One of the two siblings underwent liver transplantation in early childhood due to biliary atresia. Both patients were found to carry a homozygous missense pathogenic variant, c.242G>A (p.Arg81His), in CLDN1. The variant resulted in decreased CLDN1 expression in patient skin. 3D protein modeling predicted that p.Arg81His induces deleterious conformational changes. Accordingly, HaCaT cells transfected with a construct expressing the mutant CLDN1 cDNA featured decreased levels and mislocation of CLDN1 as compared with cells expressing the wildtype cDNA. In conclusion, we describe the first pathogenic missense variant in CLDN1 shown to result in ARCI.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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