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The purpose of this systematic review is to critically assess the evidence supporting a functional role of DNA methylation in phenotypes associated with hearing loss.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The search strategy yielded a total of 661 articles. After quality assessment, 25 records were selected (12 human DNA methylation studies, 5 experimental animal studies and 8 studies reporting mutations in the <jats:italic>DNMT1<\/jats:italic> gene). Although some methylation studies reported significant differences in CpG methylation in diverse gene promoters associated with complex hearing loss phenotypes (ARHI, otosclerosis, MD), only one study included a replication cohort that supported a regulatory role for CpG methylation in the genes <jats:italic>TCF25<\/jats:italic> and <jats:italic>POLE<\/jats:italic> in ARHI. Conversely, several studies have independently confirmed pathogenic mutations within exon 21 of the <jats:italic>DNMT1<\/jats:italic> gene, which encodes the DNA (cytosine-5)-methyltransferase 1 enzyme. This methylation enzyme is strongly associated with a rare disease defined by autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Of note, rare variants in <jats:italic>DNMT1<\/jats:italic> and <jats:italic>DNMT3A<\/jats:italic> genes have also been reported in noise-induced hearing loss.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Evidence supporting a functional role for DNA methylation in hearing loss is limited to few genes in complex disorders such as ARHI. Mutations in the <jats:italic>DNMT1<\/jats:italic> gene are associated with ADCA-DN, suggesting the CpG methylation in hearing loss genes deserves further attention in hearing research.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-024-01697-9","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T14:44:49Z","timestamp":1720190689000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A systematic review on the contribution of DNA methylation to hearing loss"],"prefix":"10.1186","volume":"16","author":[{"given":"Vibha","family":"Patil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Perez-Carpena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Lopez-Escamez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"1697_CR1","doi-asserted-by":"publisher","first-page":"16094","DOI":"10.1038\/nrdp.2016.94","volume":"3","author":"AM Korver","year":"2017","unstructured":"Korver AM, Smith RJ, Van Camp G, Schleiss MR, Bitner-Glindzicz MA, Lustig LR, et al. 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