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However, the full spectrum of\n                    <jats:italic>ODAD1<\/jats:italic>\n                    -associated pathogenesis remains incompletely defined. Here, we identified one novel homozygous loss-of-function\n                    <jats:italic>ODAD1<\/jats:italic>\n                    variant, c.705_706insGCAG, and a recurrent homozygous splicing variant, c.-41-2A\u2009&gt;\u2009C, in seven unrelated patients. These patients exhibited hallmark PCD symptoms with reduced nasal nitric oxide levels and situs inversus. Patient-derived nasal epithelial cells and air\u2012liquid interface (ALI) cultures exhibited a markedly reduced ciliary beating frequency and severe motility defects. Transmission electron microscopy and cryo-electron microscopy showed a complete loss of outer dynein arms and docking complexes, with variant-specific ultrastructural abnormalities. Unexpectedly,\n                    <jats:italic>ODAD1<\/jats:italic>\n                    deficiency also led to reduced multiciliated cells (MCCs) abundance, misoriented basal bodies, and impaired multiciliogenesis. Proteomic profiling and immunostaining revealed prominent actin cytoskeletal remodeling, including aberrant F-actin bundling throughout the epithelial layers. Pharmacological inhibition of actin polymerization using cytochalasin B partially rescued the abundance of MCCs and multiciliogenesis, indicating that actin dysregulation is a modifiable consequence of\n                    <jats:italic>ODAD1<\/jats:italic>\n                    loss. Finally, lentiviral re-expression of wild-type\n                    <jats:italic>ODAD1<\/jats:italic>\n                    in patient-derived organoids restored ODA assembly and rescued coordinated ciliary beating, confirming the pathogenicity of the identified variants. Our data reveal a dual role for ODAD1 in regulating both axonemal structure and epithelial cytoskeletal integrity and identify actin dysregulation as a previously unrecognized, targetable pathological mechanism of\n                    <jats:italic>ODAD1<\/jats:italic>\n                    -associated PCD.\n                  <\/jats:p>","DOI":"10.1038\/s41421-026-00875-8","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:45:37Z","timestamp":1774935937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia"],"prefix":"10.1038","volume":"12","author":[{"given":"Chunxiao","family":"Huo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhe","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weize","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9113-8029","authenticated-orcid":false,"given":"Miao","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-8169","authenticated-orcid":false,"given":"Shanshan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"875_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.semcdb.2020.11.007","volume":"110","author":"M Legendre","year":"2021","unstructured":"Legendre, M., Zaragosi, L. 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