{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:31:25Z","timestamp":1780583485656,"version":"3.54.1"},"reference-count":21,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is characterized by cutaneous syndactyly of the toes and fingers and abnormalities of the hair and teeth, variably associated with nail dystrophy and palmoplantar keratoderma (PPK). EDSS1 is caused by biallelic mutations in the NECTIN4 gene, encoding the adherens junction component nectin-4. Nine EDSS1 cases have been described to date. We report a 5.5-year-old female child affected with EDSS1 due to the novel homozygous frameshift mutation c.1150delC (p.Gln384ArgfsTer7) in the NECTIN4 gene. The patient presents brittle scalp hair, sparse eyebrows and eyelashes, widely spaced conical teeth and dental agenesis, as well as toenail dystrophy and mild PPK. She has minimal proximal syndactyly limited to toes 2\u20133, which makes the phenotype of our patient peculiar as the overt involvement of both fingers and toes is typical of EDSS1. All previously described mutations are located in the nectin-4 extracellular portion, whereas p.Gln384ArgfsTer7 occurs within the cytoplasmic domain of the protein. This mutation is predicted to affect the interaction with afadin, suggesting that impaired afadin activation is sufficient to determine EDSS1. Our case, which represents the first report of a NECTIN4 mutation with toe-only minimal syndactyly, expands the phenotypic and molecular spectrum of EDSS1.<\/jats:p>","DOI":"10.3390\/genes12050748","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T02:31:34Z","timestamp":1621218694000},"page":"748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ectodermal Dysplasia-Syndactyly Syndrome with Toe-Only Minimal Syndactyly Due to a Novel Mutation in NECTIN4: A Case Report and Literature Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0722-9898","authenticated-orcid":false,"given":"Roberta","family":"Rotunno","sequence":"first","affiliation":[{"name":"Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-9825","authenticated-orcid":false,"given":"Andrea","family":"Diociaiuti","sequence":"additional","affiliation":[{"name":"Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-5906","authenticated-orcid":false,"given":"Maria Lisa","family":"Dentici","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Bambino Ges\u00f9 Children Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-3314","authenticated-orcid":false,"given":"Martina","family":"Rinelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Callea","sequence":"additional","affiliation":[{"name":"Dentistry Unit, Bambino Ges\u00f9 Children Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Retrosi","sequence":"additional","affiliation":[{"name":"Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Zambruno","sequence":"additional","affiliation":[{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-849X","authenticated-orcid":false,"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Functional Genomics Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-4797","authenticated-orcid":false,"given":"May","family":"El Hachem","sequence":"additional","affiliation":[{"name":"Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/ajmg.1320530207","article-title":"Ectodermal dysplasias: A clinical classification and a causal review","volume":"53","author":"Pinheiro","year":"1994","journal-title":"Am. 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