New insight into human ciliopathy

"5 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," explains Dr. Oegema.

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. Ten years ago it was discovered that hydrolethalus syndrome results from mutations in the HYLS1 gene, located on the long arm of chromosome #11.

Dr. Oegema and colleagues now show 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 HYLS-1 stably incorporates into centrioles during their assembly, and plays a crucial role in the early step steps of the ciliogenesis pathway. Interestingly, however, HYLS-1 is dispensable for centriole assembly and centrosome function during cell division.

Their work expands the range of previously recognized human ciliopathies - which vary from polycystic kidney disease to male infertility and obesity - and establish hydrolethalus syndrome as one of the most severe ciliopathies identified to date.

Source: Cold Spring Harbor Laboratory (news : web)