{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T05:31:25Z","timestamp":1778045485765,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T00:00:00Z","timestamp":1686355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund of the European Union","award":["T2EDK-Milksafe"],"award-info":[{"award-number":["T2EDK-Milksafe"]}]},{"name":"Greek national funds","award":["T2EDK-Milksafe"],"award-info":[{"award-number":["T2EDK-Milksafe"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Ankyloblepharon-ectodermal defects-cleft lip\/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G&gt;T; p.Gly600Val). We discuss the phenotype\u2013genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel \u03b1 helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein\u2013protein interactions, thus affecting the clinical phenotype.<\/jats:p>","DOI":"10.3390\/genes14061246","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:28:21Z","timestamp":1686533301000},"page":"1246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Modeling Analysis Provides Genotype\u2013Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome"],"prefix":"10.3390","volume":"14","author":[{"given":"Anna","family":"Douka","sequence":"first","affiliation":[{"name":"Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"Laboratory of Molecular Genetics, Cephalogenetics Center, 17675 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambros","family":"Goutzanis","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Dentistry, National Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-6102","authenticated-orcid":false,"given":"Dimitrios","family":"Vlachakis","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 11855 Athens, Greece"},{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Choremion Laboratory, \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Choremion Laboratory, \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-186X","authenticated-orcid":false,"given":"Christos","family":"Yapijakis","sequence":"additional","affiliation":[{"name":"Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"Laboratory of Molecular Genetics, Cephalogenetics Center, 17675 Athens, Greece"},{"name":"University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Choremion Laboratory, \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2133.1976.tb04384.x","article-title":"The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: An autosomal dominant condition","volume":"94","author":"Hay","year":"1976","journal-title":"Br. 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