{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:19Z","timestamp":1787027659204,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2013\/08028-1"],"award-info":[{"award-number":["2013\/08028-1"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2014\/13071-6"],"award-info":[{"award-number":["2014\/13071-6"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2018\/03433-9"],"award-info":[{"award-number":["2018\/03433-9"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["406943\/2018-4"],"award-info":[{"award-number":["406943\/2018-4"]}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2013\/08028-1"],"award-info":[{"award-number":["2013\/08028-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2014\/13071-6"],"award-info":[{"award-number":["2014\/13071-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2018\/03433-9"],"award-info":[{"award-number":["2018\/03433-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["406943\/2018-4"],"award-info":[{"award-number":["406943\/2018-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Audiology Research"],"abstract":"<jats:p>Waardenburg syndrome (WS) is characterized by hearing loss and pigmentary abnormalities of the eyes, hair, and skin. The condition is genetically heterogeneous, and is classified into four clinical types differentiated by the presence of dystopia canthorum in type 1 and its absence in type 2. Additionally, limb musculoskeletal abnormalities and Hirschsprung disease differentiate types 3 and 4, respectively. Genes PAX3, MITF, SOX10, KITLG, EDNRB, and EDN3 are already known to be associated with WS. In WS, a certain degree of molecularly undetected patients remains, especially in type 2. This study aims to pinpoint causative variants using different NGS approaches in a cohort of 26 Brazilian probands with possible\/probable diagnosis of WS1 (8) or WS2 (18). DNA from the patients was first analyzed by exome sequencing. Seven of these families were submitted to trio analysis. For inconclusive cases, we applied a targeted NGS panel targeting WS\/neurocristopathies genes. Causative variants were detected in 20 of the 26 probands analyzed, these being five in PAX3, eight in MITF, two in SOX10, four in EDNRB, and one in ACTG1 (type 2 Baraitser-Winter syndrome, BWS2). In conclusion, in our cohort of patients, the detection rate of the causative variant was 77%, confirming the superior detection power of NGS in genetically heterogeneous diseases.<\/jats:p>","DOI":"10.3390\/audiolres14010002","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T05:36:12Z","timestamp":1703136972000},"page":"9-25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Waardenburg Syndrome: The Contribution of Next-Generation Sequencing to the Identification of Novel Causative Variants"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-0582","authenticated-orcid":false,"given":"William","family":"Bertani-Torres","sequence":"first","affiliation":[{"name":"Centro de Estudos sobre o Genoma Humano e C\u00e9lulas Tronco, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"},{"name":"Department of Embryology and Genetics of Malformations, INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale) UMR (Unit\u00e9 Mixte de Recherche) 1163, Universit\u00e9 Paris-Cit\u00e9 and Institut Imagine, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-9789","authenticated-orcid":false,"given":"Karina","family":"Lezirovitz","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Lab-LIM 32, Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-6044","authenticated-orcid":false,"given":"Danillo","family":"Alencar-Coutinho","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Lab-LIM 32, Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliete","family":"Pardono","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias da Sa\u00fade, Universidade Paulista UNIP, S\u00e3o Paulo 04026-002, Brazil"},{"name":"Col\u00e9gio Miguel de Cervantes, S\u00e3o Paulo 05618-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Souza","family":"da Costa","sequence":"additional","affiliation":[{"name":"Centro de Estudos sobre o Genoma Humano e C\u00e9lulas Tronco, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa do Nascimento","family":"Antunes","sequence":"additional","affiliation":[{"name":"Centro de Estudos sobre o Genoma Humano e C\u00e9lulas Tronco, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judite","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"M\u00e9decine G\u00e9nomique des Maladies Rares, AP-HP, H\u00f4pital Necker-Enfants Malades, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Alberto","family":"Otto","sequence":"additional","affiliation":[{"name":"Centro de Estudos sobre o Genoma Humano e C\u00e9lulas Tronco, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7064-0765","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Pingault","sequence":"additional","affiliation":[{"name":"Department of Embryology and Genetics of Malformations, INSERM (Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale) UMR (Unit\u00e9 Mixte de Recherche) 1163, Universit\u00e9 Paris-Cit\u00e9 and Institut Imagine, 75015 Paris, France"},{"name":"M\u00e9decine G\u00e9nomique des Maladies Rares, AP-HP, H\u00f4pital Necker-Enfants Malades, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina C\u00e9lia","family":"Mingroni-Netto","sequence":"additional","affiliation":[{"name":"Centro de Estudos sobre o Genoma Humano e C\u00e9lulas Tronco, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","first-page":"195","article-title":"A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with 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