CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

Panizzi, Jennifer R. and Becker-Heck, Anita and Castleman, Victoria H. and Al-Mutairi, Dalal A. and Liu, Yan and Loges, Niki T. and Pathak, Narendra and Austin-Tse, Christina and Sheridan, Eamonn and Schmidts, Miriam and Olbrich, Heike and Werner, Claudius and Häffner, Karsten and Hellman, Nathan and Chodhari, Rahul and Gupta, Amar and Kramer-Zucker, Albrecht and Olale, Felix and Burdine, Rebecca D. and Schier, Alexander F. and O'Callaghan, Christopher and Chung, Eddie M. K. and Reinhardt, Richard and Mitchison, Hannah M. and King, Stephen M. and Omran, Heymut and Drummond, Iain A.. (2012) CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nature Genetics, 44 (6). pp. 714-719.

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Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell and Developmental Biology (Schier)
UniBasel Contributors:Schier, Alexander F
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Nov 2021 16:08
Deposited On:23 Nov 2021 16:08

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