ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry

Am J Hum Genet. 2013 Aug 8;93(2):357-67. doi: 10.1016/j.ajhg.2013.06.009. Epub 2013 Jul 11.


The motive forces for ciliary movement are generated by large multiprotein complexes referred to as outer dynein arms (ODAs), which are preassembled in the cytoplasm prior to transport to the ciliary axonemal compartment. In humans, defects in structural components, docking complexes, or cytoplasmic assembly factors can cause primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease and defects in laterality. By using combined high resolution copy-number variant and mutation analysis, we identified ARMC4 mutations in twelve PCD individuals whose cells showed reduced numbers of ODAs and severely impaired ciliary beating. Transient suppression in zebrafish and analysis of an ENU mouse mutant confirmed in both model organisms that ARMC4 is critical for left-right patterning. We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Armadillo Domain Proteins / genetics*
  • Armadillo Domain Proteins / metabolism
  • Axoneme / genetics
  • Axoneme / metabolism
  • Axoneme / pathology
  • Body Patterning / genetics*
  • Cilia / genetics*
  • Cilia / metabolism
  • Cilia / pathology
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Dyneins / genetics*
  • Dyneins / metabolism
  • Gene Expression Regulation
  • Humans
  • Kartagener Syndrome / genetics*
  • Kartagener Syndrome / metabolism
  • Kartagener Syndrome / pathology
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Respiratory System / metabolism*
  • Respiratory System / pathology
  • Zebrafish / genetics
  • Zebrafish / metabolism


  • ARMC4 protein, mouse
  • Armadillo Domain Proteins
  • Microtubule-Associated Proteins
  • ODAD1 protein, human
  • ODAD2 protein, human
  • Dyneins