{"id":13430,"date":"2026-03-24T08:07:22","date_gmt":"2026-03-24T08:07:22","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=8a72c0ddc2bbf999977e437f7dcfe568"},"modified":"2026-03-24T08:07:22","modified_gmt":"2026-03-24T08:07:22","slug":"comprehensive-genotype-phenotype-correlation-analysis-in-11-509-neonates-carrying-common-deafness-associated-pathogenic-variants","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/24\/comprehensive-genotype-phenotype-correlation-analysis-in-11-509-neonates-carrying-common-deafness-associated-pathogenic-variants\/","title":{"rendered":"Comprehensive genotype-phenotype correlation analysis in 11 509 neonates carrying common deafness-associated pathogenic variants"},"content":{"rendered":"<sec><st>Background<\/st><p>This study aimed to analyse the distribution and genotype-phenotype correlations of pathogenic variants among 11 509 newborns carrying at least one common deafness-associated variant.<\/p><\/sec><sec><st>Methods<\/st><p>A genotype distribution analysis was performed on 11 509 neonates identified as carriers of &ge;1 pathogenic variant across four common deafness genes (<I>GJB2<\/I>, <I>SLC26A4<\/I>, <I>MT-RNR1<\/I> and <I>GJB3<\/I>) at our centre between January 2022 and December 2024. Hearing outcomes were assessed through a comprehensive evaluation protocol, initial screening (&gt;48 hour after birth, before discharge), re-screening at 42 days and diagnostic evaluation by 3 months. Sanger sequencing identified potential compound heterozygous variants, and genotype-phenotype analysis was performed on infants with hearing loss (HL).<\/p><\/sec><sec><st>Results<\/st><p>Among the 11 509 newborns carrying &ge;1 pathogenic variant, two high-risk groups were identified: 653 newborns (5.67%) carrying biallelic pathogenic variants in <I>GJB2<\/I> and 113 newborns (0.98%) carrying the <I>MT-RNR1<\/I> m.1555A&gt;G or m.1494C&gt;T variants. However, only 58 infants were confirmed with HL, and 15.52% of these passed the initial hearing screening. Sanger sequencing reclassified 23.08% of presumed heterozygotes with HL as compound heterozygotes. Acoustic diagnostic results showed that <I>GJB2<\/I> c.235del homozygotes exhibited higher HL incidence (50% vs 6.51%) and more severe\/profound HL (66.67% vs 7.14%) than <I>GJB2<\/I> c.109G&gt;A homozygotes.<\/p><\/sec><sec><st>Conclusions<\/st><p>Our data demonstrated that while genetic screening readily identifies infants with hereditary deafness susceptibility, newborn hearing screening fails to detect most of these high-risk cases due to the absence or delayed onset of HL. This gap obligates long-term audiological monitoring and highlights genetic testing&rsquo;s critical role in enabling early surveillance for later-onset HL.<\/p><\/sec>","protected":false},"excerpt":{"rendered":"<p>BackgroundThis study aimed to analyse the distribution and genotype-phenotype correlations of pathogenic variants among 11 509 newborns carrying at least one common deafness-associated variant.MethodsA genotype distribution analysis was performed on 11&#8230;<\/p>\n","protected":false},"author":501,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8,9],"tags":[],"class_list":["post-13430","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13430","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/501"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=13430"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13430\/revisions"}],"predecessor-version":[{"id":13431,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/13430\/revisions\/13431"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=13430"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=13430"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=13430"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}