Research Highlights

Mutation in ciliary disease mapped

Published online 26 January 2012

Hazem Zohny


The genetic roots of disorders affecting how the antenna-like cilia of cells work remain only partially understood; with less than half of cases linked to genes. A new study published in Nature Genetics has identified mutations in the gene CEP41 as a cause of Joubert syndrome (JBTS), a rare disorder that affects the cerebellum, the part of the brain that controls balance and coordination.

The study also implicates changes in the protein tubulin – which forms the microtubules that, among other things, form the cytoskeleton of cilia — to the pathogenesis of human ciliary diseases.

The researchers mapped a genetic region in the human genome related to JBTS (JBTS15) and identified mutations in CEP41 in five members of a consanguineous family in Egypt affected by JBTS, as well as a second Egyptian family identified by Maha Zaki, a geneticist at the National Research Centre, Cairo. Fibroblasts, the cells that form connective tissue, were unable to produce the CEP41 protein in family members with JBTS.

In a zebrafish model, CEP41 was expressed in various ciliary organs implicated in JBTS. Human CEP41 engineered into the disease-causing mutations failed to rescue the zebrafish morphant phenotype, in which the gene encoding CEP41 was suppressed during embryonic development.


  1. Eun Lee, J. et al. CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium. Nature Genetics (2011) doi:10.1038/ng.1078