{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T09:09:54Z","timestamp":1770541794175,"version":"3.49.0"},"reference-count":11,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centro AMES"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Ectodermal dysplasia (ED) encompasses a heterogeneous group of genetic disorders affecting ectoderm-derived structures such as hair, teeth, nails, and sweat glands. Among these, variants in TSPEAR (Thrombospondin-type laminin G domain and epilepsy-associated repeats) have been implicated in autosomal recessive ED type 14 (OMIM 618180), predominantly manifesting with dental anomalies and hair dysplasia. However, the mutational spectrum of TSPEAR remains incompletely characterized. Methods: Two female siblings (ID#1 and ID#4) were clinically evaluated for ED. Genetic analysis, including next-generation sequencing (NGS) and Sanger validation, was conducted to identify TSPEAR variants. A segregation study confirmed inheritance patterns within the family. Results: Both affected siblings exhibited hallmark features of TSPEAR-related ED14, including oligodontia with dysmorphic, pointed maxillary central incisors. Hair thinning and cutaneous angiomas were predominant in ID#4. Genetic analysis identified two compound heterozygous variants in TSPEAR: c.543-1G&gt;A, a splice-site variant likely to disrupt mRNA processing, and NM_144991.2:c.1251G&gt;C(p.Gln417His), a missense variant with predicted deleterious effects. Segregation analysis confirmed maternal and paternal inheritance of the respective variants. A third sibling, ID#5, was identified as a heterozygous carrier without clinical manifestations. Conclusions: This study contributes to the expanding understanding of TSPEAR-related ED14 by providing novel genotype\u2013phenotype correlations.<\/jats:p>","DOI":"10.3390\/genes16050519","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:50:17Z","timestamp":1745992217000},"page":"519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expanding the Mutational Spectrum of TSPEAR in Ectodermal Dysplasia Type 14: A Familial Case Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Roberto","family":"Sirica","sequence":"first","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-3855","authenticated-orcid":false,"given":"Alessandro","family":"Ottaiano","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via Mariano Semmola, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele De","family":"Brasi","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera di Rilievo Nazionale, \u201cSantobono Pausilipon\u201d, Via Teresa Ravaschieri 8, 80122 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Marcella","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Acquaviva","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera di Rilievo Nazionale, \u201cSantobono Pausilipon\u201d, Via Teresa Ravaschieri 8, 80122 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Ianniello","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5131-9528","authenticated-orcid":false,"given":"Nadia","family":"Petrillo","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Istituto Comprensivo Statale \u201cMassimo Troisi\u201d, Via Pini di Solimena 31, 80046 San Giorgio a Cremano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossana","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7004-9633","authenticated-orcid":false,"given":"Eloisa","family":"Evangelista","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Fico","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5274-3989","authenticated-orcid":false,"given":"Giovanni","family":"Savarese","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100186","DOI":"10.1016\/j.xhgg.2023.100186","article-title":"Genomics England Research Consortium; Solve-RD consortium; Varshney GK, Banka, S. 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