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Biallelic <jats:italic>MITF<\/jats:italic> mutations have been found associated with a rare hearing loss syndrome consisting eye abnormalities and albinism; and a more severe type of WS whose heterozygous parents were affected with classic WS in both cases. The aims of this study were to identify a new candidate gene causing autosomal recessive nonsyndromic hearing loss (ARNSHL) and confirm its causation by finding additional families affected with the candidate gene and supporting evidences from functional analyses. By using whole exome sequencing, we identified a homozygous c.1022G&gt;A: p.Arg341His variant of <jats:italic>MITF<\/jats:italic>, which co-segregated with the hearing loss in five affected children of a consanguineous hearing couple. Targeted exome sequencing in a cohort of 130 NSHL individuals, using our in-house gene panel revealed a second family with c.1021C&gt;T: p.Arg341Cys <jats:italic>MITF<\/jats:italic> variant. Functional studies confirmed that the Arg341His and Arg341Cys alleles yielded a normal sized MITF protein, with aberrant cytosolic localization as supported by the molecular model and the reporter assay. In conclusion, we demonstrate <jats:italic>MITF<\/jats:italic> as a new cause of ARNSHL, with heterozygous individuals free of symptoms. <jats:italic>MITF<\/jats:italic> should be included in clinical testing for NSHL, though it is rare.<\/jats:p>","DOI":"10.1038\/s41598-020-69633-4","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T10:04:12Z","timestamp":1596017052000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["MITF variants cause nonsyndromic sensorineural hearing loss with autosomal recessive inheritance"],"prefix":"10.1038","volume":"10","author":[{"given":"Supranee","family":"Thongpradit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natini","family":"Jinawath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Javed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saisuda","family":"Noojarern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthaporn","family":"Khongkraparn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thipwimol","family":"Tim-Aroon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisna","family":"Lertsukprasert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhoom","family":"Suktitipat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laran T.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duangrurdee","family":"Wattanasirichaigoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"69633_CR1","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.otc.2015.06.005","volume":"48","author":"KW Chang","year":"2015","unstructured":"Chang, K. 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