CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Anne Christine Merveille, Erica Ellen Davis, Anita Becker-Heck, Marie Legendre, Israel Amirav, Géraldine Bataille, John Belmont, Nicole Beydon, Frédéric Billen, Annick Clément, Cécile Clercx, André Coste, Rachelle Crosbie, Jacques De Blic, Stephane Deleuze, Philippe Duquesnoy, Denise Escalier, Estelle Escudier, Manfred Fliegauf, Judith HorvathKent Hill, Mark Jorissen, Jocelyne Just, Andreas Kispert, Mark Lathrop, Niki Tomas Loges, June K. Marthin, Yukihide Momozawa, Guy Montantin, Kim G. Nielsen, Heike Olbrich, Jean François Papon, Isabelle Rayet, Gilles Roger, Miriam Schmidts, Henrique Tenreiro, Jeffrey A. Towbin, Diana Zelenika, Hanswalter Zentgraf, Michel Georges*, Anne Sophie Lequarré, Elias Nicholas Katsanis, Heymut Omran, Serge Amselem

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalNature Genetics
Volume43
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Genetics

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