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In our previous study, we have identified a de novo heterozygous mutation \u2212832G\u2009&gt;\u2009A in the promoter of TGFB1 in an otosclerosis patient. In the present study, we progressively screened this mutation in a cohort of 254 cases and 262 controls. The family members of the patient positive for \u2212832G\u2009&gt;\u2009A variation were also screened and found inheritance of this variation only to her daughter. Interestingly, this variation is associated with a decreased level of the TGFB1 transcript in the patient compared to her parents and controls. <jats:italic>In silico<\/jats:italic> analysis of this mutation predicted the altered binding of two transcription factors v-Myb and MZF1 in the mutated promoter sequence. Further, functional analysis of this mutation using <jats:italic>in vitro<\/jats:italic> luciferase and electrophoretic mobility shift assays revealed that this variation is associated with decreased gene expression. In conclusion, this study established the fact that TGFB1 mutation \u2212832G\u2009&gt;\u2009A altered the TGFB1 promoter activity, which could affect the susceptibility to otosclerosis development. Further, systemic analysis of TGFB1 gene sequence and expression analysis of this gene might reveal its precise role in the pathogenesis of otosclerosis.<\/jats:p>","DOI":"10.1038\/srep29572","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T14:20:27Z","timestamp":1468333227000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Otosclerosis Associated with a De Novo Mutation \u2212832G\u2009&gt;\u2009A in the TGFB1 Gene Promoter Causing a Decreased Expression Level"],"prefix":"10.1038","volume":"6","author":[{"given":"Saurabh","family":"Priyadarshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirtal","family":"Hansdah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay Sundar","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan Chandra","family":"Biswal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puppala Venkat","family":"Ramchander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,11]]},"reference":[{"key":"BFsrep29572_CR1","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1359\/jbmr.071112","volume":"23","author":"I Schrauwen","year":"2008","unstructured":"Schrauwen, I. et al. 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