In vivo study a novel ribosomopathy with severe developmental defects using C. elegans models

This is a new collaborative project between two research groups within the CERMO-FC aimed to advance our knowledge of the cellular consequences occurring in SHQ1-linked dystonia, and ribosomopathies in general. Mutations in SHQ1 have been recently identified in a few children in Canada and Australia, as well as in Austria, Saudi Arabia, and the USA, and can lead to growth delays and severe neurological disorders, including seizures (this condition remains an orphan disease, lacking an ORPHANET designation). We anticipate that SHQ1-linked dystonia will soon join the group of recognized ribosomopathies, which are genetic disorders caused by mutations in genes essential for the biogenesis or function of ribosomes (incidence <1/100,000). Well-known ribosomopathies include Diamond-Blackfan anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome, yet our understanding of the molecular mechanisms driving these diseases remains poor. We are investigating an entirely novel orphan disease, expected to generate new insights into the function of SQH1, by providing the first characterization of its role in an animal, using C. elegans models for mutations corresponding to D175Y and E292K in humans, and determining the neuromuscular consequences. This will provide important information for predicting pathogenicity, while finding potential prognostic markers for tailoring therapies.

Laboratory of Pre Claire Bénard and Pr François Dragon (UQAM)
Laureate: 2024 Collaborative Research Grant