Pilot study for Unveiling ZNF865 role in undiagnosed rare neurodevelopmental disease (PUZZLE)

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2023 Biomedical sciences have made great strides in the study of rare genetic diseases but still today there are undiagnosed syndromes or disease-gene mutations whose biological significance is unknown. Our project aims to unravel yet unknown aspects of a syndrome that clinically presents developmental delay, intellectual disabilities, reduced muscle tone and altered craniofacial features associated with de novo mutations in the ZNF865 gene. To date we have very little information on the function of this gene in humans or other species. It is therefore necessary to be able to expand our knowledge in order to better characterize the pathology and to be able to envisage therapeutic indications for the future. For our preliminary studies we will use the zebrafish as animal model, that shares with humans the genomic structure of this gene and its expression during embryonic development and in the adult brain. We will use in zebrafish embryos the CRISPR/Cas13 technology that will allow us to verify if the partial lack of znf865 function causes the developmental abnormalities seen in patients. We believe that this pilot project can provide valuable information that would allow us to plan in the near future the generation of genetic models of the disease to reveal new aspects of this undiagnosed rare disease and to plan drug screening and therapeutic approaches.