{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:23:12Z","timestamp":1790439792009,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The diagnosis of an ectodermal dysplasia (ED) is often made by dermatologists. Some of the more than 50 distinct ectodermal dysplasias, however, are still largely unknown and their pathogenesis is poorly understood. Since we recently discovered that variants of the Interferon Regulatory Factor 6 (IRF6) gene\n                    <jats:italic>IRF6<\/jats:italic>\n                    may cause ED, we have further investigated the link between this gene and maldevelopment of tissues originating from the embryonic ectoderm. Disease characterization in two previously reported subjects and one newly identified patient (mosaic status) included systematic clinical and genetic evaluation, assessment of all available patient records and dental radiographs, hearing tests and immunostaining of skin samples. Structural models of native and mutant IRF6 were analysed to elucidate the pathogenesis. IRF6\u2010associated ED, a combination of natal teeth (irregularly), absent sweat glands, hidradenitis suppurativa\u2010like symptoms, onychodysplasia, agenesis of numerous deciduous and permanent teeth, and sensorineural hearing impairment, was linked to amino acid substitutions in a region between the DNA\u2010binding domain and the protein\u2010binding domain of IRF6, which has not yet been assigned a function. Genotype\u2013phenotype correlations from a total of five patients and immunohistochemical data support the assumption that IRF6\u2010associated ED is based on a gain\u2010of\u2010function mechanism. Thus,\n                    <jats:italic>IRF6<\/jats:italic>\n                    variants are not only the cause of Van der Woude syndrome and popliteal pterygium syndrome, two diseases with cleft lip\/palate as common features, but are most likely responsible also for a new, challenging syndrome without orofacial clefting. Our results facilitate accurate and early diagnosis in affected individuals and may pave the way for specific treatment.\n                  <\/jats:p>","DOI":"10.1111\/exd.70331","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:57:59Z","timestamp":1784789879000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep Phenotyping and Molecular Elucidation of a New Syndrome: Ectodermal Dysplasia Caused by\n                    <scp>\n                      <i>IRF6<\/i>\n                    <\/scp>\n                    Variants"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8548-4053","authenticated-orcid":false,"given":"Holm","family":"Schneider","sequence":"first","affiliation":[{"name":"Center for Ectodermal Dysplasias University Hospital Erlangen  Erlangen Germany"},{"name":"Department of Pediatrics Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-7106","authenticated-orcid":false,"given":"Smail","family":"Hadj\u2010Rabia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reference Centre for Genodermatoses and Rare Skin Diseases (FIMARAD) Hopital Necker\u2010Enfants Malades, INSERM 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0229-8931","authenticated-orcid":false,"given":"Carola","family":"Berking","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4820-6158","authenticated-orcid":false,"given":"Matthias","family":"Weider","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Orofacial Orthopedics Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5259-4144","authenticated-orcid":false,"given":"Julie","family":"Steffann","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Hopital Necker\u2010Enfants Malades, INSERM 1163, Institut Imagine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J.","family":"Rieker","sequence":"additional","affiliation":[{"name":"Department of Pathology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen 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