{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:02:21Z","timestamp":1788498141843,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to assess the prevalence of genetic variants associated with hearing loss in a large cohort of children in Canada using high throughput next generation sequencing (NGS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 485 children with hearing loss underwent NGS testing with an 80 gene panel of syndromic and non\u2010syndromic variants known to be associated with hearing loss. Genetic variants were classified as pathogenic, likely pathogenic, likely benign, benign, or variants of uncertain significance (VUS), according to the American College of Medical Genetics and Genomics guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Across the 80 genes tested, 923 variants, predominantly in 28 genes, were identified in 324 children. Pathogenic variants occurred in 19\/80 (23.8%) of the hearing loss related genes tested and confirmed the etiology of hearing loss in 73\/485 (15.1%) of children. <jats:italic>GJB2<\/jats:italic> was the most prevalent gene, affecting 28\/73 (38.4%) children with confirmed genetic hearing loss in our cohort. Most identified variants (748\/923, 81.0%, in 76\/80 genes) were of uncertain significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic testing using NGS identified the etiology in approximately 15% of childhood hearing loss in a Canadian cohort which is lower than what is typically reported. <jats:italic>GJB2<\/jats:italic> was the most common genetic cause of hearing loss. VUS are commonly identified, presenting clinical challenges for counseling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>4 <jats:italic>Laryngoscope<\/jats:italic>, 134:3832\u20133838, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.31373","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T09:07:04Z","timestamp":1709284024000},"page":"3832-3838","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Variants in Genes Associated with Hearing Loss in Children: Prevalence in a Large Canadian Cohort"],"prefix":"10.1002","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5664-1653","authenticated-orcid":false,"given":"Emily R.","family":"Wener","sequence":"first","affiliation":[{"name":"Archie's Cochlear Implant Laboratory, Neuroscience &amp; Mental Health Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob D.","family":"McLennan","sequence":"additional","affiliation":[{"name":"Archie's Cochlear Implant Laboratory, Neuroscience &amp; Mental Health Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake C.","family":"Papsin","sequence":"additional","affiliation":[{"name":"Archie's Cochlear Implant Laboratory, Neuroscience &amp; Mental Health Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of Toronto, Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Cushing","sequence":"additional","affiliation":[{"name":"Archie's Cochlear Implant Laboratory, Neuroscience &amp; Mental Health Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of Toronto, Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri James","family":"Stavropoulos","sequence":"additional","affiliation":[{"name":"Genome Diagnostics Paediatric Laboratory Medicine, Clinical and Metabolic Genetics The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Mendoza\u2010Londono","sequence":"additional","affiliation":[{"name":"Genome Diagnostics Paediatric Laboratory Medicine, Clinical and Metabolic Genetics The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Quercia","sequence":"additional","affiliation":[{"name":"Division of Clinical &amp; Metabolic Genetics The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Genetic Counselling The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Molecular Genetics, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-3125","authenticated-orcid":false,"given":"Karen A.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Archie's Cochlear Implant Laboratory, Neuroscience &amp; Mental Health Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of Toronto, Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0911225"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050700"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2015.03.008"},{"key":"e_1_2_6_5_1","unstructured":"Newborn Screening Ontario.Risk factor screening for permanent hearing loss in Ontario. 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