{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:26Z","timestamp":1787028566326,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Madrid, Spain","doi-asserted-by":"publisher","award":["PI20\/00619"],"award-info":[{"award-number":["PI20\/00619"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII), Madrid, Spain","doi-asserted-by":"publisher","award":["PI24\/00397"],"award-info":[{"award-number":["PI24\/00397"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"European Union","doi-asserted-by":"publisher","award":["PI20\/00619"],"award-info":[{"award-number":["PI20\/00619"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"European Union","doi-asserted-by":"publisher","award":["PI24\/00397"],"award-info":[{"award-number":["PI24\/00397"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hearing impairments (HIs) are clinically and genetically very heterogeneous. Finding the causative mutations in patients is frequently a challenge. We investigated two brothers affected by a sensorineural, moderate non-syndromic HI. Exome sequencing revealed that they carried the heterozygous c.812C&gt;T (p.Ser271Leu) variant in GATA3. This gene encodes a transcription factor involved in embryonic development, its mutations causing the autosomal dominant HDR (hypoparathyroidism, deafness, and renal disease) syndrome. The variant affects a conserved residue within the proximal zinc-finger motif of GATA3. Sanger sequencing confirmed the presence of the variant in the two brothers, but it showed that surprisingly it was not carried by any of the parents. Segregation studies on 20 fully informative microsatellite markers in the family confirmed that the variant arose de novo. A benign SNP in the mother, close to the position of the variant, allowed us to determine that this was inherited from the father. Gene reporter functional assays supported the pathogenicity of the variant. Clinical reassessment of the two brothers did not disclose any additional abnormality. We conclude that mosaicism for this de novo mutation in the father\u2019s germ line explains the pattern of inheritance in this family and that p.Ser271Leu is causing this unexpected phenotype of non-syndromic HI.<\/jats:p>","DOI":"10.3390\/ijms26136363","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:11:04Z","timestamp":1751429464000},"page":"6363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["De Novo Heterozygous GATA3 Missense Variant Causes an Unexpected Phenotype of Non-Syndromic Hearing Impairment with Apparently Recessive Inheritance"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-0370","authenticated-orcid":false,"given":"Mar\u00eda","family":"Dom\u00ednguez-Ruiz","sequence":"first","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-1087","authenticated-orcid":false,"given":"Gema","family":"Garrido","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1695-5250","authenticated-orcid":false,"given":"Paz","family":"Mart\u00ednez-Beneyto","sequence":"additional","affiliation":[{"name":"ENT Department, Hospital Cl\u00ednico Universitario, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico de Valencia (INCLIVA), 46010 Valencia, Spain"},{"name":"Surgery Department, Universitat de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-4320","authenticated-orcid":false,"given":"Francisco J.","family":"del Castillo","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Villamar","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"G\u00f3mez-Rosas","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3839-5098","authenticated-orcid":false,"given":"Miguel A.","family":"Moreno-Pelayo","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1188-3665","authenticated-orcid":false,"given":"Ignacio","family":"del Castillo","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41576-023-00597-7","article-title":"Deafness: From Genetic Architecture to Gene Therapy","volume":"24","author":"Petit","year":"2023","journal-title":"Nat. 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