{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:58:02Z","timestamp":1773053882960,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    (chr. 21q22.3) encodes a protein involved in tooth development and is predominantly expressed in the enamel knot. Biallelic loss of function variants in\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    cause ectodermal dysplasia, tooth agenesis and sensorineural hearing loss. However, the role of\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    in auditory processes is unclear. This study aimed at better delineating the allelic and clinical spectrum of\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    \u2010associated disorders. We identified homozygous and compound heterozygous causative variants in\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    [NM_144991.3] in 11 patients from seven families. Abnormalities in tooth number and shape (conical teeth and tooth agenesis with a variable number of missing teeth) were found in all affected individuals. Maxillary retrusion was present in 6\/11. Manifestations in other ectodermal\u2010derived organs were seen in a minority of patients. None of the individuals had hearing loss. We identified a total of 10 variants, of which seven have not been previously published, and analyzed the effect of missense variants to support their pathogenicity. Our results demonstrate that individuals with biallelic variants in\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    show complete penetrance for dental manifestations, but not for other ectodermal abnormalities.\n                    <jats:italic>TSPEAR<\/jats:italic>\n                    \u2010related disorder is more common than previously thought, while hearing loss is not a feature of the disease.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64304","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:00:45Z","timestamp":1762430445000},"page":"790-799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotypes and Phenotypes of Patients With\n                    <i>TSPEAR<\/i>\n                    \u2010Related Disorder: Evidence of a Predominant Dental Phenotype"],"prefix":"10.1002","volume":"200","author":[{"given":"Debora","family":"Vergani","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Tiberi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annarita","family":"Giliberti","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Meyer Children's Hospital IRCCS  Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-6464","authenticated-orcid":false,"given":"Elia","family":"Dirupo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Meyer Children's Hospital IRCCS  Florence 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USL\u2010IRCCS di Reggio Emilia  Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences University of L'Aquila  L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7684-3982","authenticated-orcid":false,"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Azienda USL\u2010IRCCS di Reggio Emilia  Reggio Emilia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Virginia","family":"Gulino","sequence":"additional","affiliation":[{"name":"USL Umbria 1  Assisi Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Mariani","sequence":"additional","affiliation":[{"name":"Mariani Foundation Center for the Fragile Child, Pediatric Unit ASST Lariana  Como 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