Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Nat Genet 2014 Jun 01;466:646-51. doi: 10.1038/ng.2961.
Show Gene links Show Anatomy links

Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia.

Wallmeier J , Al-Mutairi DA , Chen CT , Loges NT , Pennekamp P , Menchen T , Ma L , Shamseldin HE , Olbrich H , Dougherty GW , Werner C , Alsabah BH , Köhler G , Jaspers M , Boon M , Griese M , Schmitt-Grohé S , Zimmermann T , Koerner-Rettberg C , Horak E , Kintner C , Alkuraya FS , Omran H .

Using a whole-exome sequencing strategy, we identified recessive CCNO (encoding cyclin O) mutations in 16 individuals suffering from chronic destructive lung disease due to insufficient airway clearance. Respiratory epithelial cells showed a marked reduction in the number of multiple motile cilia (MMC) covering the cell surface. The few residual cilia that correctly expressed axonemal motor proteins were motile and did not exhibit obvious beating defects. Careful subcellular analyses as well as in vitro ciliogenesis experiments in CCNO-mutant cells showed defective mother centriole generation and placement. Morpholino-based knockdown of the Xenopus ortholog of CCNO also resulted in reduced MMC and centriole numbers in embryonic epidermal cells. CCNO is expressed in the apical cytoplasm of multiciliated cells and acts downstream of multicilin, which governs the generation of multiciliated cells. To our knowledge, CCNO is the first reported gene linking an inherited human disease to reduced MMC generation due to a defect in centriole amplification and migration.

PubMed ID: 24747639
Article link: Nat Genet
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ccno mcidas
GO keywords: motile cilium assembly
Morpholinos: ccno MO1

Disease Ontology terms: ciliopathy [+]
References [+] :
Abecasis, An integrated map of genetic variation from 1,092 human genomes. 2012, Pubmed