{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:09:03Z","timestamp":1773828543750,"version":"3.50.1"},"reference-count":45,"publisher":"BMJ","issue":"12","funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM007748"],"award-info":[{"award-number":["T32 GM007748"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["K08-DC016034"],"award-info":[{"award-number":["K08-DC016034"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,7,15]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>It is well established that biallelic mutations in transmembrane protease, serine 3 (<jats:italic>TMPRSS3<\/jats:italic>) cause hearing loss. Currently, there is controversy regarding the audiological outcomes after cochlear implantation (CI) for <jats:italic>TMPRSS3<\/jats:italic>-associated hearing loss. This controversy creates confusion among healthcare providers regarding the best treatment options for individuals with <jats:italic>TMPRSS3<\/jats:italic>-related hearing loss.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A literature review was performed to identify all published cases of patients with <jats:italic>TMPRSS3<\/jats:italic>-associated hearing loss who received a CI. CI outcomes of this cohort were compared with published adult CI cohorts using postoperative consonant-nucleus-consonant (CNC) word performance. <jats:italic>TMPRSS3<\/jats:italic> expression in mouse cochlea and human auditory nerves (HAN) was determined by using hybridisation chain reaction and single-cell RNA-sequencing analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In aggregate, 27 patients (30 total CI ears) with <jats:italic>TMPRSS3<\/jats:italic>-associated hearing loss treated with CI, and 85% of patients reported favourable outcomes. Postoperative CNC word scores in patients with <jats:italic>TMPRSS3<\/jats:italic>-associated hearing loss were not significantly different than those seen in adult CI cohorts (8 studies). Robust <jats:italic>Tmprss3<\/jats:italic> expression occurs throughout the mouse organ of Corti, the spindle and root cells of the lateral wall and faint staining within &lt;5% of the HAN, representing type II spiral ganglion neurons. Adult HAN express negligible levels of <jats:italic>TMPRSS3<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The clinical features after CI and physiological expression of <jats:italic>TMPRSS3<\/jats:italic> suggest against a major role of TMPRSS3 in auditory neurons.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108654","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T13:25:18Z","timestamp":1660310718000},"page":"1219-1226","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear 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