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Archive - Aug 4, 2009

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New Cilia Disease Identified

Scientists have shown that a lethal developmental disorder (hydolethalus syndrome) belongs to an emerging class of human ciliopathic disorders that includes polycystic kidney disease. "Five years ago, a human genetics study linked hydrolethalus syndrome to a mutation in a protein named HYLS1. Since this discovery, the function of HYLS1 has remained unknown. Our work solves this mystery, showing that HYLS1 is a centriolar protein required for the formation of cilia, small hair-like cellular projections that execute a variety of essential motile and sensory functions," explained Dr. Karen Oegema, an author of the study. Hydrolethalus syndrome is a rare genetic disorder characterized by severe birth defects (hydrocephalus, polydactyly, cardio/pulmonary malformations) that result in stillbirth or early neonatal death. The majority of cases affect people of Finnish ancestry, where the incidence is roughly 1 in 20,000. In the current work, Dr. Oegema and colleagues showed that the evolutionarily conserved HYLS1 protein is, in fact, a centriolar protein that is specifically required for cilia formation in both C. elegans and vertebrates. The researchers demonstrated that HYLS1 stably incorporates into centrioles during their assembly, and plays a crucial role in the early steps of the ciliogenesis pathway. Interestingly, however, HYLS1 is dispensable for centriole assembly and centrosome function during cell division. This work is reported in the September 1 issue of Genes & Development. [Press release]