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We present the results of a two-year period of molecular diagnosis that included 207 French families referred for non-syndromic hearing loss. Our multi-step strategy involved (i) <jats:italic>DFNB1<\/jats:italic> locus analysis, (ii) MPS of 74 genes, and (iii) additional approaches including Copy Number Variations, <jats:italic>in silico<\/jats:italic> analyses, minigene studies coupled when appropriate with complete gene sequencing, and a specific assay for <jats:italic>STRC<\/jats:italic>. This comprehensive screening yielded an overall diagnostic rate of 48%, equally distributed between <jats:italic>DFNB1<\/jats:italic> (24%) and the other genes (24%). Pathogenic genotypes were identified in 19 different genes, with a high prevalence of <jats:italic>GJB2<\/jats:italic>, <jats:italic>STRC<\/jats:italic>, <jats:italic>MYO15A<\/jats:italic>, <jats:italic>OTOF<\/jats:italic>, <jats:italic>TMC1<\/jats:italic>, <jats:italic>MYO7A<\/jats:italic> and <jats:italic>USH2A<\/jats:italic>. Involvement of an Usher gene was reported in 16% of the genotyped cohort. Four <jats:italic>de novo<\/jats:italic> variants were identified. This study highlights the need to develop several molecular approaches for efficient molecular diagnosis of hearing loss, as this is crucial for genetic counselling, audiological rehabilitation and the detection of syndromic forms.<\/jats:p>","DOI":"10.1038\/s41598-017-16846-9","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T14:16:17Z","timestamp":1511792177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-1221","authenticated-orcid":false,"given":"D.","family":"Baux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Vach\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Blanchet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Baudoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Moclyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Faug\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Touraine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Isidor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Dupin-Deguine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Nizon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mercier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Calais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Azher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Perdomo-Trujillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Giuliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Claustres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Koenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mondain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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