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Murine ossicle micromorphology of the <jats:italic>ENPP1<\/jats:italic><jats:sup><jats:italic>asj\/asj<\/jats:italic><\/jats:sup> mutant compared to wild-type.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Setting<\/jats:title>\n                <jats:p>Clinical research hospital; basic science laboratory.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Participants<\/jats:title>\n                <jats:p>Nineteen individuals with GACI who met clinical, biochemical, and genetic criteria for diagnosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Main outcomes and measures<\/jats:title>\n                <jats:p>Clinical, biochemical, and radiologic features associated with hearing status.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Pure-tone thresholds could be established in 15 (n\u2009=\u200930 ears) of the 19 patients who underwent audiological assessments. The prevalence of HL was 50% (15\/30) of ears, with conductive HL in 80% and sensorineural HL in 20%. In terms of patients with HL (n\u2009=\u20098), seven patients had bilateral HL and one patient had unilateral HL. Degree of HL was mild to moderate for 87% of the 15 ears with hearing loss. Of those patients with sufficient pure-tone and middle ear function data, 80% (8\/10) had audiometric configurations suggestive of ossicular chain dysfunction (OCD). Recurrent episodes of otitis media (ROM) requiring pressure-equalizing tube placement were common. In patients who underwent cranial CT, 54.5% (6\/11) had auricular calcification. Quantitative backscattered electron imaging (qBEI) of murine ossicles supports an OCD component of auditory dysfunction in GACI, suggesting loss of ossicular osteocytes without initiation of bone remodeling.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions and relevance<\/jats:title>\n                <jats:p>Hearing loss is common in GACI; it is most often conductive, and mild to moderate in severity. The etiology of HL is likely multifactorial, involving dysfunction of the ossicular chain and\/or recurrent otitis media. Clinically, this study highlights the importance of early audiologic and otologic evaluation in persons with GACI. Novel findings of high rates of OCD and ROM may inform management, and in cases of unclear HL etiology, dedicated temporal bone imaging should be considered.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-022-02410-w","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T11:06:59Z","timestamp":1658228819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI)"],"prefix":"10.1186","volume":"17","author":[{"given":"Elizabeth H.","family":"Theng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen C.","family":"Brewer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Oheim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher K.","family":"Zalewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly A.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximillian M.","family":"Delsmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Rolvien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel I.","family":"Gafni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demetrios T.","family":"Braddock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Jeffrey Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-1046","authenticated-orcid":false,"given":"Carlos R.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"issue":"2","key":"2410_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1161\/circgenetics.108.797704","volume":"1","author":"F Rutsch","year":"2008","unstructured":"Rutsch F, B\u00f6yer P, Nitschke Y, et al. 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These studies were conducted in accordance with the Declaration of Helsinki and protocols were approved by the NIH Institutional Review Board (IRB). All subjects or their guardians provided informed consent and assent when appropriate. Consent for publication is included within the research protocols.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval, consent to participate, and consent for publication"}},{"value":"C.R.F. and R.I.G. report a collaboration with Inozyme Pharma, Inc as part of a Cooperative Research and Development Agreement. D.T.B. is an inventor of patents owned by Yale University for therapeutics treating ENPP1 deficiency. D.T.B is an equity holder and receives research and consulting support from Inozyme Pharma, Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"273"}}