2. Academic Validation
  3. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

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

  • Nat Genet. 2012 May 13;44(6):714-9. doi: 10.1038/ng.2277.
Jennifer R Panizzi 1,  Anita Becker-Heck,  Victoria H Castleman,  Dalal A Al-Mutairi,  Yan Liu,  Niki T Loges,  Narendra Pathak,  Christina Austin-Tse,  Eamonn Sheridan,  Miriam Schmidts,  Heike Olbrich,  Claudius Werner,  Karsten Häffner,  Nathan Hellman,  Rahul Chodhari,  Amar Gupta,  Albrecht Kramer-Zucker,  Felix Olale,  Rebecca D Burdine,  Alexander F Schier,  Christopher O'Callaghan,  Eddie M K Chung,  Richard Reinhardt,  Hannah M Mitchison,  Stephen M King,  Heymut Omran,  Iain A Drummond
Affiliations

Affiliation

  • 1 Nephrology Division, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
PMID: 22581229 DOI: 10.1038/ng.2277
Abstract

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.

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