{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:00Z","timestamp":1791352200035,"version":"4.3.1"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Waardenburg syndrome (WS) is a neurocristopathy primarily characterized by congenital hearing loss and multisystem pigmentary abnormalities. We report a 12-year-old Han Chinese girl who presented with moderate-to-severe sensorineural hearing loss, a wide nasal root, diffuse hypopigmentation of the hair, and facial freckles\u2014features partially similar to the WS phenotype. However, her calculated W-index was 1.87, below the diagnostic threshold for dystopia canthorum (&amp;gt;1.95), and her overall clinical presentation did not meet the diagnostic criteria for any WS subtype. Whole-exome sequencing (WES) and subsequent familial Sanger sequencing identified a homozygous\n                    <jats:italic>GJB2<\/jats:italic>\n                    variant, c.109G\u2009&amp;gt;\u2009A (p.Val37Ile), in the proband, with both parents confirmed as heterozygous carriers. Based on the integrated clinical and genetic evidence, the patient was diagnosed with\n                    <jats:italic>GJB2<\/jats:italic>\n                    -related autosomal recessive nonsyndromic hearing loss (DFNB1A). Her WS-like features were interpreted as a possible phenocopy. This case highlights that in patients with hearing loss exhibiting incomplete or atypical WS features, comprehensive genetic testing\u2014including analysis of\n                    <jats:italic>GJB2<\/jats:italic>\n                    \u2014is crucial to differentiate phenocopies, establish an accurate etiology, and provide a basis for precise diagnosis and genetic counseling.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1925409","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:40Z","timestamp":1791348760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A homozygous variant in the GJB2 gene as a potential phenocopy of Waardenburg syndrome: case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuehua","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimeng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Xie","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longnian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1136\/jmg.34.8.656","article-title":"Waardenburg syndrome","volume":"34","author":"Read","year":"1997","journal-title":"J Med Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7143458","DOI":"10.1155\/2019\/7143458","article-title":"New genotypes and phenotypes in patients with 3 subtypes of Waardenburg syndrome identified by diagnostic next-generation sequencing","volume":"2019","author":"Li","year":"2019","journal-title":"Neural Plast"},{"key":"B3","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3390\/ijms27010127","article-title":"Genetics of Waardenburg syndrome in Africa: a systematic review","volume":"27","author":"Aboagye","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/humu.21211","article-title":"Review and update of mutations causing Waardenburg syndrome","volume":"31","author":"Pingault","year":"2010","journal-title":"Hum Mutat"},{"key":"B5","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s00439-021-02405-w","article-title":"A common founder effect of the splice site variant c.-23\u2009+\u20091G\u2009>\u2009A in GJB2 gene causing autosomal recessive deafness 1A (DFNB1A) in Eurasia","volume":"141","author":"Solovyev","year":"2022","journal-title":"Hum Genet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3390\/ijms27010491","article-title":"GJB2-related hearing loss: genotype-phenotype correlations, natural history, and emerging therapeutic strategies","volume":"27","author":"Morris","year":"2026","journal-title":"Int J Mol Sci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/cge.13468","article-title":"Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome","volume":"95","author":"Somashekar","year":"2019","journal-title":"Clin Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1038\/s41436-019-0535-9","article-title":"Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen hearing loss expert panel","volume":"21","author":"Shen","year":"2019","journal-title":"Genet Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.jmoldx.2023.07.005","article-title":"Genetic factors contribute to the phenotypic variability in GJB2-related hearing impairment","volume":"25","author":"Chiang","year":"2023","journal-title":"J Mol Diagn"},{"key":"B10","doi-asserted-by":"publisher","first-page":"6371082","DOI":"10.1155\/humu\/6371082","article-title":"Whole genome sequencing improves the identification of pathogenic and novel variation in nonsyndromic hearing loss","volume":"2025","author":"Rentas","year":"2025","journal-title":"Hum Mutat"},{"key":"B11","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.gim.2021.12.007","article-title":"Biallelic p.V37I variant in GJB2 is associated with increasing incidence of hearing loss with age","volume":"24","author":"Chen","year":"2022","journal-title":"Genet Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"475","DOI":"10.2174\/138920211797904098","article-title":"GJB2 gene mutations in syndromic skin diseases with sensorineural hearing loss","volume":"12","author":"Iossa","year":"2011","journal-title":"Curr Genomics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.bbrc.2010.05.066","article-title":"Novel mutations of PAX3, MITF, and SOX10 genes in Chinese patients with type I or type II Waardenburg syndrome","volume":"397","author":"Chen","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.jgg.2011.11.003","article-title":"A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II","volume":"38","author":"Yan","year":"2011","journal-title":"J Genet Genomics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/ajmg.1320550123","article-title":"Waardenburg syndrome type II: phenotypic findings and diagnostic criteria","volume":"55","author":"Liu","year":"1995","journal-title":"Am J Med Genet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41434-021-00240-2","article-title":"Genetic insights, disease mechanisms, and biological therapeutics for Waardenburg syndrome","volume":"29","author":"Huang","year":"2022","journal-title":"Gene Ther"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1925409\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:41Z","timestamp":1791348761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1925409\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":16,"alternative-id":["10.3389\/fmed.2026.1925409"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1925409","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1925409"}}