{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:09:30Z","timestamp":1766362170237,"version":"3.37.3"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2013-0825"],"award-info":[{"award-number":["2013-0825"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre"},{"DOI":"10.13039\/501100001645","name":"Boehringer Ingelheim Fonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Diaphanous related formins are regulatory cytoskeletal protein involved in actin elongation and microtubule stabilization. In humans, defects in two of the three diaphanous genes (<jats:italic>DIAPH1<\/jats:italic>and<jats:italic>DIAPH3<\/jats:italic>) have been associated with different types of hearing loss. Here, we investigate the role of the third member of the family,<jats:italic>DIAPH2<\/jats:italic>, in nonsyndromic hearing loss, prompted by the identification, by exome sequencing, of a predicted pathogenic missense variant in<jats:italic>DIAPH2<\/jats:italic>. This variant occurs at a conserved site and segregated with nonsyndromic X-linked hearing loss in an Italian family. Our immunohistochemical studies indicated that the mouse ortholog protein Diaph2 is expressed during development in the cochlea, specifically in the actin-rich stereocilia of the sensory outer hair cells.<jats:italic>In-vitro<\/jats:italic>studies showed a functional impairment of the mutant DIAPH2 protein upon RhoA-dependent activation. Finally,<jats:italic>Diaph2<\/jats:italic>knock-out and knock-in mice were generated by CRISPR\/Cas9 technology and auditory brainstem response measurements performed at 4, 8 and 14 weeks. However, no hearing impairment was detected. Our findings indicate that<jats:italic>DIAPH2<\/jats:italic>may play a role in the inner ear; further studies are however needed to clarify the contribution of<jats:italic>DIAPH2<\/jats:italic>to deafness.<\/jats:p>","DOI":"10.1371\/journal.pone.0273586","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T18:25:46Z","timestamp":1674498346000},"page":"e0273586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["In-depth genetic and molecular characterization of diaphanous related formin 2 (DIAPH2) and its role in the inner ear"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-8317","authenticated-orcid":true,"given":"Chiara","family":"Chiereghin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Robusto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-8600","authenticated-orcid":true,"given":"Morag 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