Targeted gene under study:
PAK1, OMIM: # 618158
Abstract
Missense variants in the PAK1 gene have been described in a small number of patients. These individuals presented with macrocephaly, neurodevelopmental disorders including intellectual disability and epilepsy. Ataxia also appears to be a common feature. Functional studies on certain variants suggest that their pathogenicity can be attributed to a gain-of-function mechanism. To further investigate this gene and its associated syndrome, we have assembled a cohort of six French patients with PAK1 missense variants through the AnDDi-Rares rare disease network. These patients exhibit phenotypes similar to those previously described. We aim to collect as many cases as possible across Europe to refine the phenotype description, understand the underlying mechanisms, and potentially propose a therapeutic intervention. We are also in contact with a research team studying these variations in murine models. The ultimate goal of this call for collaboration is to publish a medical paper by the end of the year 2024. We rely on your collaboration for the success of this project.
Coordinating clinicians
Dr William DUFOUR (geneticist) – william.dufour@chu-lyon.fr
Lionel HEISER (genetics resident) – lionel.heiser@chu-lyon.fr
Institution
Genetics Dept, CHU of Lyon (Hospices Civils de Lyon), Lyon, France
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: No
3- Linked to a translational/basic research project: No