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These disorders show overlapping phenotypic characteristics with various combinations of the following features: ectodermal dysplasia, split-hand\/foot malformation\/syndactyly, lacrimal duct obstruction, hypoplastic breasts and\/or nipples, ankyloblepharon filiforme adnatum, hypospadias and cleft lip\/palate. We describe a family with six individuals presenting with a striking novel phenotype characterized by a furrowed or cleft tongue, a narrow face, reddish hair, freckles and various foot deformities. Whole-exome sequencing (WES) identified a novel heterozygous variant, c.3G&gt;T, in<jats:italic>TP63<\/jats:italic>affecting the translation initiation codon (p.1Met?). Sanger sequencing confirmed dominant inheritance of this unique variant in all six affected family members. In summary, our findings indicate that heterozygous variants in<jats:italic>TP63<\/jats:italic>affecting the first translation initiation codon result in a novel phenotype dominated by a cleft tongue, expanding the complex genotypic and phenotypic spectrum of<jats:italic>TP63<\/jats:italic>-associated disorders.<\/jats:p>","DOI":"10.1038\/s41431-021-00967-x","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:03:09Z","timestamp":1633914189000},"page":"211-218","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Familial cleft tongue caused by a unique translation initiation codon variant in TP63"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5942-2924","authenticated-orcid":false,"given":"Julia","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudrun","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Kaulfu\u00df","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Funke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Wilken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2777-0198","authenticated-orcid":false,"given":"G\u00f6khan","family":"Yigit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-0364","authenticated-orcid":false,"given":"Bernd","family":"Wollnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"967_CR1","unstructured":"Sutton VR, van Bokhoven H. 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