{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:15:29Z","timestamp":1772496929204,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in the \u03b3\u2010secretase enzyme subunits have been described in multiple kindreds with familial hidradenitis suppurativa (<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>In this study, we report a novel nicastrin (<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content>)<\/jats:italic>mutation causing<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>in a Dutch family. We sought to explore the immunobiological function of<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>mutations using data of the Immunological Genome Project.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood samples of three affected and two unaffected family members were collected. Whole\u2010genome sequencing was performed using genomic<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>isolated from peripheral blood leucocytes. Sanger sequencing was done to confirm the causative<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>variant and the familial segregation. The microarray data set of the Immunological Genome Project was used for thorough dissection of the expression and function of wildtype<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>in the immune system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a family consisting of 23 members, we found an autosomal dominant inheritance pattern of<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>and detected a novel splice site mutation (c.1912_1915del<jats:styled-content style=\"fixed-case\">CAGT<\/jats:styled-content>) in the<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>gene resulting in a frameshift and subsequent premature stop. All affected individuals had<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>lesions on non\u2010flexural and atypical locations. Wildtype<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>appears to be upregulated in myeloid cells like monocytes and macrophages, and in mesenchymal cells such as fibroblastic reticular cells and fibroblasts. In addition, within the 25 highest co\u2010expressed genes with<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>we identified<jats:italic><jats:styled-content style=\"fixed-case\">CAPNS<\/jats:styled-content>1<\/jats:italic>,<jats:italic><jats:styled-content style=\"fixed-case\">ARNT<\/jats:styled-content><\/jats:italic>and<jats:italic><jats:styled-content style=\"fixed-case\">PPARD<\/jats:styled-content><\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reports the identification a novel<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>gene splice site mutation which causes familial<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>. The associated immunobiological functions of<jats:italic><jats:styled-content style=\"fixed-case\">NCSTN<\/jats:styled-content><\/jats:italic>and its co\u2010expressed genes<jats:italic><jats:styled-content style=\"fixed-case\">ARNT<\/jats:styled-content><\/jats:italic>and<jats:italic><jats:styled-content style=\"fixed-case\">PPARD<\/jats:styled-content><\/jats:italic>link genetics to the most common environmental and metabolic<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>risk factors which are smoking and obesity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.16310","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T16:08:46Z","timestamp":1582214926000},"page":"2353-2361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A novel nicastrin mutation in a three\u2010generation Dutch family with hidradenitis suppurativa: a search for functional 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