{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:33:26Z","timestamp":1761647606173},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,1,2]],"date-time":"2009-01-02T00:00:00Z","timestamp":1230854400000},"content-version":"vor","delay-in-days":123,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objective\/Hypothesis:<\/jats:bold> Otosclerotic bone is supposed to show unique CD46 expression pattern because otosclerosis is an organ\u2010specific disease with viral etiology.<\/jats:p><jats:p><jats:bold>Study Design:<\/jats:bold> Otosclerosis is a complex bone remodeling disorder of the human otic capsule, which is associated with persisting measles virus infection. The general cellular receptor of measles virus is the CD46, which has 14\u2010known splicing isoforms.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Nucleic acid was extracted from ankylotic stapes footplates (N = 99) removed during stapedectomies. Consecutive histological, CD46 specific immunohistologic analysis, and multiple polymerase chain reaction (PCR) amplifications were performed. Measles virus was detected by seminested reverse transcriptase\u2010PCR. Splicing variants of CD46 were identified by nested reverse transcriptase\u2010PCR and finally determined by mass sequencing of complementary DNA.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Measles virus RNA was detectable only in histologically otosclerotic stapes footplates. Virus negative\u2010fixed stapes represent degenerative disorders of variable histopathology. Otosclerosis is featured by an increased number of osteoclasts showing strong CD46 immunoreaction in contrast to nonotosclerotic stapes fixations. Normal and nonotosclerotic stapes footplates show consistent expression of \u201cc,\u201d \u201cd,\u201d \u201ce,\u201d \u201cf,\u201d and \u201cl\u201d CD46 splicing isoforms. In contrast, four novel CD46 splicing variants were additionally detected in otosclerosis: <jats:italic>os1<\/jats:italic>, <jats:italic>os2<\/jats:italic>, <jats:italic>os3<\/jats:italic>, and <jats:italic>os4<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Newly described CD46 isoforms have shorter or missing transmembrane domain and a rare cytoplasmic tail with pathological or uncommon signal transduction; however, virus binding ability remains equal and invariable. These changes may be responsible for the smooth virus replication. A special expression pattern and altered functions of CD46 could explain the organ\u2010specific and virus\u2010associated pathogenesis of otosclerosis.<\/jats:p>","DOI":"10.1097\/mlg.0b013e31817c133d","type":"journal-article","created":{"date-parts":[[2008,8,27]],"date-time":"2008-08-27T07:18:27Z","timestamp":1219821507000},"page":"1669-1676","source":"Crossref","is-referenced-by-count":28,"title":["Disease\u2010Associated Novel CD46 Splicing Variants and Pathologic Bone Remodeling in Otosclerosis"],"prefix":"10.1002","volume":"118","author":[{"given":"Tam\u00e1s","family":"Karosi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Szalm\u00e1s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Csomor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f3zsef","family":"K\u00f3nya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mih\u00e1ly","family":"Petk\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Sziklai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,2]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016489509139314"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/000348940111001001"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200407000-00009"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200103000-00023"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(02)00679-8"},{"key":"e_1_2_7_7_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0030-6665(20)30813-6","article-title":"Histopathology 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