{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:55:50Z","timestamp":1773417350456,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":218,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Sensorineural hearing loss is a prevalent disorder with significant genetic involvement, which is often challenging to diagnose due to genetic heterogeneity. Exome sequencing (ES) has been a standard diagnostic tool for sensorineural hearing loss, but its limitations in detecting copy number variants (CNVs) and intronic variants have prompted the exploration of genome sequencing (GS) for improved diagnostic yield. We conducted GS on 46 hearing loss families with previously negative ES results and an additional cohort of 36 patients with a monoallelic pathogenic variant in <jats:italic>GJB2<\/jats:italic> (the most common deafness gene). Additionally, the impact of a previously unrecognized novel 125\u2010kb deletion in the DFNB1 locus on <jats:italic>GJB2<\/jats:italic> expression was assessed using quantitative polymerase chain reaction (qPCR), and haplotype analysis was performed to characterize the deletion. GS diagnosed eight cases (17%, 8\/46) in the ES\u2010negative cohort, primarily attributed to CNVs (6\/8). Notably, a previously unrecognized 125\u2009kb deletion in the DFNB1 region was identified, affecting <jats:italic>GJB2<\/jats:italic> expression and characterizing it as a founder effect in East Asian. In 47 patients with a monoallelic <jats:italic>GJB2<\/jats:italic> variant, 15% (95% CI, 7.4%\u201328%) were diagnosed with DFNB1 deletions. Analysis of the gnomAD database revealed the prevalence and ethnic diversity of DFNB1 deletions, with the novel 125\u2009kb deletion emerging as a prominent pathogenic variant in East Asian, non\u2010Finnish European, and admixed American populations. Our study highlights the utility of GS in diagnosing sensorineural hearing loss. The identification of DFNB1 deletions underscores their significant contribution to hearing loss etiology, advocating for their inclusion in routine diagnostic testing. We propose GS as a primary genetic testing approach for patients with hearing loss, offering comprehensive genomic analysis and the potential for improved diagnostic accuracy.<\/jats:p>","DOI":"10.1155\/2024\/9517114","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T12:07:51Z","timestamp":1722946071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genome Sequencing Unveils the Role of Copy Number Variants in Hearing Loss and Identifies Novel Deletions With Founder Effect in the DFNB1 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