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In two families, NM_017780.4: c.3553A\u2009&gt;\u2009G [p.(Met1185Val)] and c.5390G\u2009&gt;\u2009C [p.(Gly1797Ala)] were detected as monoallelic <jats:italic>CHD7<\/jats:italic> variants in patients with EVA. At least one subject from each family had additional signs or potential signs of CHARGE syndrome but did not meet diagnostic criteria for CHARGE. In silico modeling of these two missense substitutions predicted detrimental effects upon CHD7 protein structure. Consistent with a role of CHD7 in this tissue, <jats:italic>Chd7<\/jats:italic> transcript and protein were detected in all epithelial cells of the endolymphatic duct and sac of the developing mouse inner ear. These results suggest that some <jats:italic>CHD7<\/jats:italic> variants can cause nonsyndromic hearing loss and EVA. <jats:italic>CHD7<\/jats:italic> should be included in DNA sequence analyses to detect pathogenic variants in EVA patients. <jats:italic>Chd7<\/jats:italic> expression and mutant phenotype data in mice suggest that CHD7 contributes to the formation or function of the endolymphatic sac and duct.<\/jats:p>","DOI":"10.1007\/s00439-023-02581-x","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:02:22Z","timestamp":1693918942000},"page":"1499-1517","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CHD7 variants associated with hearing loss and enlargement of the vestibular aqueduct"],"prefix":"10.1007","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-7520","authenticated-orcid":false,"given":"Isabelle","family":"Roux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-8891","authenticated-orcid":false,"given":"Cristina","family":"Fenollar-Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6568-5053","authenticated-orcid":false,"given":"Hyun Jae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-8807","authenticated-orcid":false,"given":"Parna","family":"Chattaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5205-7293","authenticated-orcid":false,"given":"Ivan A.","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2290-4858","authenticated-orcid":false,"given":"Kyungreem","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-8539","authenticated-orcid":false,"given":"Keiji","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-049X","authenticated-orcid":false,"given":"Carmen C.","family":"Brewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-9195","authenticated-orcid":false,"given":"John A.","family":"Butman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1537-7356","authenticated-orcid":false,"given":"Robert J.","family":"Morell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8070-2007","authenticated-orcid":false,"given":"Donna M.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5684-3109","authenticated-orcid":false,"given":"Andrew J.","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"2581_CR1","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s004319900409","volume":"159","author":"V Abadie","year":"2000","unstructured":"Abadie V, Wiener-Vacher S, Morisseau-Durand MP, Poree C, Amiel J, Amanou L, Peigne C, Lyonnet S, Manac\u2019h Y (2000) Vestibular anomalies in CHARGE syndrome: investigations on and consequences for postural development. 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All adult subjects provided written informed consent and minor subjects provided assent. <i>Animals.<\/i> All animal experiments and procedures were performed according to protocols approved by the joint Animal Care and Use Committee of the National Institute of Neurological Diseases and Stroke and the National Institute on Deafness and Other Communication Disorders (#1264).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}