{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nODAD1 (also known as CCDC114) is a key component of the outer dynein arm (ODA) docking complex, essential for the proper attachment and assembly of ODAs along the axoneme of motile cilia and sperm flagella. Disruption of ODAD1 function through loss‐of‐function mutations prevents the assembly of ODAs, leading to immotile cilia and classical primary ciliary dyskinesia (PCD) phenotypes characterized by chronic airway disease and laterality defects. In studies of patients with PCD, defects in ODAD1/CCDC114 were clearly linked to the absence of ODAs, thereby impairing effective ciliary beating."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent investigations have expanded the known functional repertoire of ODAD1 beyond motile cilia. Evidence now indicates that ODAD1 is localized at the basal body of primary cilia and may influence the formation and maintenance of these sensory organelles. Knockdown experiments in cellular models demonstrated that reduced ODAD1 expression correlates with a decreased number of primary cilia, thereby broadening our understanding of the protein’s role in cilia-related developmental and degenerative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, clinical studies in defined populations, such as those in Volendam, have highlighted the impact of specific CCDC114 mutations on disease severity. While complete loss of ODAD1 results in a severe PCD phenotype with significant pulmonary complications, certain non-canonical splice mutations allowing the expression of a partially functional, truncated ODAD1 protein can lead to residual ODA assembly and milder clinical outcomes. This demonstrates not only the central role of ODAD1 in ciliary motility but also suggests that even modest restoration of its function may confer therapeutic benefits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexandros Onoufriadis, Tamara Paff, Dinu Antony, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.11.002"}], "href": "https://doi.org/10.1016/j.ajhg.2012.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23261303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23261303"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael R Knowles, Margaret W Leigh, Lawrence E Ostrowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.11.003"}], "href": "https://doi.org/10.1016/j.ajhg.2012.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23261302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23261302"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ping Li, Yani He, Guangyan Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC114 is mutated in patient with a complex phenotype combining primary ciliary dyskinesia, sensorineural deafness, and renal disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-018-0514-z"}], "href": "https://doi.org/10.1038/s10038-018-0514-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30291279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30291279"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Renate Kos, Joël Israëls, Christine D L van Gogh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet C Semin Med Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.c.31968"}], "href": "https://doi.org/10.1002/ajmg.c.31968"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35343062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35343062"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lawrence E Ostrowski, Weining Yin, Amanda J Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of a Truncated Form of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ODAD1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23031753"}], "href": "https://doi.org/10.3390/ijms23031753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35163670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35163670"}]}]}]}