{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:56Z","timestamp":1787014196426,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in\n                    <jats:italic>KRT5<\/jats:italic>\n                    ,\n                    <jats:italic>POGLUT<\/jats:italic>\n                    \u2010\n                    <jats:italic>1<\/jats:italic>\n                    and\n                    <jats:italic>POFUT<\/jats:italic>\n                    \u2010\n                    <jats:italic>1<\/jats:italic>\n                    genes have been associated with DDD, and loss\u2010of\u2010function mutations in\n                    <jats:italic>PSENEN<\/jats:italic>\n                    , a subunit of the gamma\u2010secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in\n                    <jats:italic>NCSTN<\/jats:italic>\n                    , another subunit of the gamma\u2010secretase, was already described in a patient suffering from HS and DDD but whether\n                    <jats:italic>NCSTN<\/jats:italic>\n                    could be considered a novel gene for DDD is still debated. Here, we enrolled a four\u2010generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the\n                    <jats:italic>NCSTN<\/jats:italic>\n                    gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense\u2010mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the\n                    <jats:italic>NCSTN<\/jats:italic>\n                    levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma\u2010secretase complex, possibly causing DDD. Our findings clearly support\n                    <jats:italic>NCSTN<\/jats:italic>\n                    as a novel DDD gene and suggest carefully investigating this co\u2010occurrence in HS patients carrying a mutation in the\n                    <jats:italic>NCSTN<\/jats:italic>\n                    gene.\n                  <\/jats:p>","DOI":"10.1111\/exd.14919","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T08:34:51Z","timestamp":1693816491000},"page":"1935-1945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A loss\u2010of\u2010function\n                    <scp>\n                      <i>NCSTN<\/i>\n                    <\/scp>\n                    mutation associated with familial\n                    <scp>Dowling Degos disease<\/scp>\n                    and hidradenitis suppurativa"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9540-6756","authenticated-orcid":false,"given":"Ana Sofia Lima Estevao","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Keizo Asami Institute\u2010iLIKA Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Cardoso","family":"de Siqueira","sequence":"additional","affiliation":[{"name":"Hospital das Cl\u00ednicas Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Nait\u2010Meddour","sequence":"additional","affiliation":[{"name":"Univ Paris Est Cr\u00e9teil, INSERM, IMRB, Translational Neuropsychiatry  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Maura","family":"Tricarico","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2013IRCCS \"Burlo Garofolo\" Department of Advanced Diagnostics  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Moura","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2013IRCCS \"Burlo Garofolo\" Department of Advanced Diagnostics  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almerinda","family":"Agrelli","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Materials (LMNANO) Center for Strategic Technologies Northeastern (CETENE)  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adamo Pio","family":"d'Adamo","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2013IRCCS \"Burlo Garofolo\" Department of Advanced Diagnostics  Trieste Italy"},{"name":"University of Trieste Department of Medical Surgical and Health Sciences  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Jamain","sequence":"additional","affiliation":[{"name":"Univ Paris Est Cr\u00e9teil, INSERM, IMRB, Translational Neuropsychiatry  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[{"name":"LARC Laboratory Animal Research Center University of Qatar  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"de F\u00e1tima\u00a0Medeiros\u00a0Brito","sequence":"additional","affiliation":[{"name":"Hospital das Cl\u00ednicas Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9548-2254","authenticated-orcid":false,"given":"Michele","family":"Boniotto","sequence":"additional","affiliation":[{"name":"Univ Paris Est Cr\u00e9teil, INSERM, IMRB, Translational Neuropsychiatry  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Andr\u00e9 Cavalcanti","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Keizo Asami Institute\u2010iLIKA Federal University of Pernambuco  Recife Brazil"},{"name":"Department of Pathology Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.13316"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/500850"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2011.07.038"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.09741.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.12.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14273"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16603"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.10.025"},{"issue":"6","key":"e_1_2_9_11_1","first-page":"446","article-title":"Reticulate pigmented anomaly of 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