{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:21:43Z","timestamp":1772119303744,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SGH Health Development Fund","award":["SGH-HDF\/FY24\/GC(1)"],"award-info":[{"award-number":["SGH-HDF\/FY24\/GC(1)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Nonsyndromic hearing loss (NSHL) is a highly prevalent, genetically heterogeneous condition, yet its molecular basis in the Singaporean population remains underexplored. We performed whole-exome sequencing and integrative bioinformatics analysis in 115 patients with NSHL to define population-specific genetic biomarkers. A molecular diagnosis was achieved in 57% of cases, with 76% of identified variants classified as pathogenic or likely pathogenic and 24% exhibiting high pathogenic potential. Common East Asian NSHL genes, including GJB2, SLC26A4, and OTOF, were frequently detected alongside less prevalent genes such as ACTG1, CEACAM16, COL11A2, DIAPH1, KCQN4, MYH14, MYO6, MYO7A, MYO15A, SLC17A8, SMPX, STRC, TJP2, TMC1, TMPRSS3, highlighting extensive genetic heterogeneity. Notably, multiple novel variants, including MYO6 c.554-2A&gt;G, and TNC p.N750Y, were identified, expanding the known mutational spectrum of NSHL. Genotype\u2013phenotype correlations revealed that GJB2 variants were primarily associated with mild to moderate hearing loss, whereas SLC26A4 variants correlated with severe to profound phenotypes in the Singaporean populations. Collectively, our study provides important insights into the genetic architecture of NSHL in Singapore\u2019s population. In addition, it supports improved molecular diagnosis yield and informed clinical management decisions as well as the advancement of precision medicine approaches aimed at reducing the burden of hearing loss in the region.<\/jats:p>","DOI":"10.3390\/biom16030352","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:58:03Z","timestamp":1772114283000},"page":"352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Biomarkers and Mutational Landscape of Nonsyndromic Hearing Loss (NSHL) in the Singaporean Population: Clinical Translational Implications"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-0900","authenticated-orcid":false,"given":"Che Kang","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Clinical Translation Research, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"Medicine Academic Clinical Programme (ACP), Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei Shuang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Translation Research, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore 599489, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-5305","authenticated-orcid":false,"given":"Joyce Zhi\u2019en","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"Surgery Academic Clinical Programme (ACP), Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7403-1059","authenticated-orcid":false,"given":"Jia Hui","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"Surgery Academic Clinical Programme (ACP), Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni Gin","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6197-8879","authenticated-orcid":false,"given":"Pei Shan","family":"Leem","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Ann","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiun Fong","family":"Thong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa Yee Jueen","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"Surgery Academic Clinical Programme (ACP), Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization: WHO (2025, December 01). 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