CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews.
Arg81His
CLDN1
ILVASC
Moroccan Jews
cholestasis
founder variant
ichthyosis
neonatal ichthyosis and sclerosing cholangitis syndrome
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
17
09
2023
received:
22
07
2023
accepted:
26
09
2023
pubmed:
10
10
2023
medline:
10
10
2023
entrez:
10
10
2023
Statut:
ppublish
Résumé
Neonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p.Arg81His, associated with isolated skin ichthyosis phenotype, has been recently reported in a family of Moroccan Jewish descent. We now describe seven patients with ILVASC, originating from four non consanguineous families of North African Jewish ancestry (including one previously reported family), harboring CLDN1 p.Arg81His variant, and broaden the phenotypic spectrum attributed to this variant to include teeth, hair, and liver/bile duct involvement, characteristic of ILVASC. Furthermore, we provide additional evidence for pathogenicity of the CLDN1 p.Arg81His variant by transmission electron microscopy of the affected skin, revealing distorted tight junction architecture, and show through haplotype analysis in the vicinity of the CLDN1 gene, that this variant represents a founder variant in Jews of Moroccan descent with an estimated carrier frequency of 1:220.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
44-51Subventions
Organisme : Morris Kahn Family Foundation
Informations de copyright
© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
Références
Hadj-Rabia S, Baala L, Vabres P, et al. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004;127(5):1386-1390.
Feldmeyer L, Huber M, Fellmann F, Beckmann JS, Frenk E, Hohl D. Confirmation of the origin of NISCH syndrome. Hum Mutat. 2006;27(5):408-410.
Kirchmeier P, Sayar E, Hotz A, et al. Novel mutation in the CLDN1 gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome. Br J Dermatol. 2014;170(4):976-978.
Youssefian L, Vahidnezhad H, Saeidian AH, Sotoudeh S, Zeinali S, Uitto J. Gene-targeted next-generation sequencing identifies a novel CLDN1 mutation in a consanguineous family with NISCH syndrome. Am J Gastroenterol. 2017;112(2):396-398.
Szepetowski S, Lacoste C, Mallet S, Roquelaure B, Badens C, Fabre A. NISCH syndrome, a rare cause of neonatal cholestasis: a case report. Arch Pediatr. 2017;24(12):1228-1234.
Nagtzaam IF, Peeters VPM, Vreeburg M, et al. Novel CLDN1 mutation in ichthyosis-hypotrichosis-sclerosing cholangitis syndrome without signs of liver disease. Br J Dermatol. 2018;178(3):e202-e203.
Izurieta Pacheco AC, Monfort Carretero L, Prat Torres C, Garcia-Alix Perez A, Molera BC. NISCH syndrome: an extremely rare cause of neonatal cholestasis. J Hepatol. 2020;73(5):1257-1258.
Alsafri MS, Charbit-Henrion F, Lacaille F, Bourrat E, Steffann J, Hadj-Rabia S. Novel CLDN1 deletion associated with ichthyosis, sclerosing cholangitis and acquired alopecia. Acta Derm Venereol. 2020;100(13):adv00173.
Nagtzaam IF, van Geel M, Driessen A, Steijlen PM, van Steensel MA. Bile duct paucity is part of the neonatal ichthyosis-sclerosing cholangitis phenotype. Br J Dermatol. 2010;163(1):205-207.
Salik D, Hadj-Rabia S, Hohl D, et al. Evaluation of neurodevelopmental symptoms in 10 cases of neonatal ichthyosis and sclerosing cholangitis syndrome. Pediatr Dermatol. 2022;39(4):590-593.
Mohamad J, Samuelov L, Assaf S, et al. Autosomal recessive congenital ichthyosis caused by a pathogenic missense variant in CLDN1. Am J Med Genet A. 2022;188(10):2879-2887.
Paganelli M, Stephenne X, Gilis A, et al. Neonatal ichthyosis and sclerosing cholangitis syndrome: extremely variable liver disease severity from claudin-1 deficiency. J Pediatr Gastroenterol Nutr. 2011;53(3):350-354.
Yogev Y, Perez Y, Noyman I, et al. Progressive hereditary spastic paraplegia caused by a homozygous KY mutation. Eur J Hum Genet. 2017;25(8):966-972.
Seelow D, Schuelke M, Hildebrandt F, Nurnberg P. HomozygosityMapper-an interactive approach to homozygosity mapping. Nucleic Acids Res. 2009;37:W593-W599.
Grosse B, Cassio D, Yousef N, Bernardo C, Jacquemin E, Gonzales E. Claudin-1 involved in neonatal ichthyosis sclerosing cholangitis syndrome regulates hepatic paracellular permeability. Hepatology. 2012;55(4):1249-1259.
Nemeth Z, Szasz AM, Tatrai P, et al. Claudin-1, -2, -3, -4, -7, -8, and -10 protein expression in biliary tract cancers. J Histochem Cytochem. 2009;57(2):113-121.
Sakisaka S, Kawaguchi T, Taniguchi E, et al. Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology. 2001;33(6):1460-1468.
Mitic LL, Van Itallie CM, Anderson JM. Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lessons from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol. 2000;279(2):G250-G254.
Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med. 1998;339(17):1217-1227.
Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2(4):285-293.
Joao SM, Arana-Chavez VE. Tight junctions in differentiating ameloblasts and odontoblasts differentially express ZO-1, occludin, and claudin-1 in early odontogenesis of rat molars. Anat Rec A Discov Mol Cell Evol Biol. 2004;277(2):338-343.
Zorn-Kruppa M, Vidal YSS, Houdek P, et al. Tight junction barriers in human hair follicles-role of claudin-1. Sci Rep. 2018;8(1):12800.
De Benedetto A, Rafaels NM, McGirt LY, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786.
Batista DI, Perez L, Orfali RL, et al. Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol. 2015;29(6):1091-1095.
Tokumasu R, Yamaga K, Yamazaki Y, et al. Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis. Proc Natl Acad Sci U S A. 2016;113(28):E4061-E4068.
Gruber R, Bornchen C, Rose K, et al. Diverse regulation of claudin-1 and claudin-4 in atopic dermatitis. Am J Pathol. 2015;185(10):2777-2789.
Furuse M, Hata M, Furuse K, et al. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002;156(6):1099-1111.
Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141(7):1539-1550.
Gilad S, Bar-Shira A, Harnik R, et al. Ataxia-telangiectasia: founder effect among north African Jews. Hum Mol Genet. 1996;5(12):2033-2037.