{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:05:16Z","timestamp":1790168716232,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hereditary hearing loss is a genetically heterogeneous disorder posing challenges for molecular diagnosis. This study aimed to characterize the mutation spectrum, including rare and previously unreported variants, using a tiered strategy in a Han Chinese cohort from Southwest China.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective study, 43 patients underwent targeted hotspot screening, followed by whole\u2010exome sequencing in 11 patients with no hotspot variants detected. Variants were annotated and interpreted according to American College of Medical Genetics and Genomics guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Initial hotspot screening established molecular diagnoses in 23 patients based on seven pathogenic or likely pathogenic variants in\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\n                        \u2010\n                        <jats:styled-content style=\"fixed-case\">RNR1<\/jats:styled-content>\n                        ,\n                        <jats:styled-content style=\"fixed-case\">GJB2<\/jats:styled-content>\n                        , and\n                        <jats:styled-content style=\"fixed-case\">SLC26A4<\/jats:styled-content>\n                        .\n                      <\/jats:italic>\n                      Whole\u2010exome sequencing identified six additional rare variants in\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">CDH23<\/jats:styled-content>\n                        ,\n                        <jats:styled-content style=\"fixed-case\">ILDR1<\/jats:styled-content>\n                        ,\n                        <jats:styled-content style=\"fixed-case\">OTOF<\/jats:styled-content>\n                        , and\n                        <jats:styled-content style=\"fixed-case\">SLC12A2<\/jats:styled-content>\n                        ,\n                      <\/jats:italic>\n                      and established two diagnoses involving\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">ILDR1<\/jats:styled-content>\n                        and\n                        <jats:styled-content style=\"fixed-case\">CDH23<\/jats:styled-content>\n                        .\n                      <\/jats:italic>\n                      A previously unreported\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SLC12A2<\/jats:italic>\n                      <\/jats:styled-content>\n                      missense variant, c.\n                      <jats:styled-content style=\"fixed-case\">2936A<\/jats:styled-content>\n                      &gt;G (p.\n                      <jats:styled-content style=\"fixed-case\">Glu979Gly<\/jats:styled-content>\n                      ) was identified as a variant of uncertain significance and retained as a candidate finding.\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>CDH23<\/jats:italic>\n                      <\/jats:styled-content>\n                      c.\n                      <jats:styled-content style=\"fixed-case\">5311C<\/jats:styled-content>\n                      &gt;T (p.Arg1771Ter) has not previously been reported in Han Chinese patients with hearing loss, to our knowledge.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings expand the mutation spectrum of hereditary hearing loss in a Han Chinese cohort from Southwest China and highlight the practical value of a tiered testing strategy integrating targeted hotspot screening with whole\u2010exome sequencing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70291","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:31:21Z","timestamp":1789957881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutation Spectrum and Novel Rare Variants in a Han Chinese 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