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The wide divergence of WS poses significant diagnostic and management challenges. This study investigated type 4 WS within an underrepresented Mongolian population. Whole-exome sequencing revealed that two unique heterozygous variants were identified in the SOX10 gene: c.393C&gt;G (p.Asn131Lys) in a five-year-old female patient presenting with profound sensorineural hearing loss (SNHL), dystopia canthorum, and a white forelock; and c.535A&gt;T (p.Lys179Ter) in a nine-year-old male patient presenting with profound SNHL, dystopia canthorum, and Hirschsprung\u2019s disease. Temporal bone imaging revealed abnormalities in the inner ear structure in both patients. The genotypic and phenotypic characteristics were meticulously delineated, incorporating the deleterious effects of these variants, as evaluated by multiple predictive tools and the American College of Medical Genetics and Genomics (ACMG) criteria. In addition, structural characterizations were also presented using AlphaFold. The findings of this study contribute valuable genetic data to the limited literature on type 4 WS within this ethnic group and highlight the importance of genetic testing and multidisciplinary care for this rare disorder in settings with limited resources.<\/jats:p>","DOI":"10.3390\/ijms26136258","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Waardenburg Syndrome Type 4 in Mongolian Children: Genetic and Clinical Characterization"],"prefix":"10.3390","volume":"26","author":[{"given":"Bayasgalan","family":"Gombojav","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia"},{"name":"International Cyber Education Center, Graduate School, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jargalkhuu","family":"Erdenechuluun","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14170, Mongolia"},{"name":"The EMJJ Otolaryngology Hospital, Ulaanbaatar 14210, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tserendulam","family":"Batsaikhan","sequence":"additional","affiliation":[{"name":"The EMJJ Otolaryngology Hospital, Ulaanbaatar 14210, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-3667","authenticated-orcid":false,"given":"Narandalai","family":"Danshiitsoodol","sequence":"additional","affiliation":[{"name":"Department of Probiotic Sciences for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 7348551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaya","family":"Makhbal","sequence":"additional","affiliation":[{"name":"The EMJJ Otolaryngology Hospital, Ulaanbaatar 14210, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maralgoo","family":"Jargalmaa","sequence":"additional","affiliation":[{"name":"The EMJJ Otolaryngology Hospital, Ulaanbaatar 14210, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4954-9642","authenticated-orcid":false,"given":"Tuvshinbayar","family":"Jargalkhuu","sequence":"additional","affiliation":[{"name":"The EMJJ Otolaryngology Hospital, Ulaanbaatar 14210, Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue-Sheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital, Taipei 100225, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Hsuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital, Taipei 100225, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-5343","authenticated-orcid":false,"given":"Jacob Shu-Jui","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6150-4577","authenticated-orcid":false,"given":"Cheng-Yu","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University College of Medicine, Taipei 100225, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-2204","authenticated-orcid":false,"given":"Chen-Chi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital, Taipei 100225, Taiwan"},{"name":"Department of Otolaryngology, National Taiwan University College of Medicine, Taipei 100225, Taiwan"},{"name":"Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 302058, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","unstructured":"Winters, R., and Masood, S. 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