Characterisation of a PRDX5 nonsense mutation associated with a neurodevelopmental syndrome by Marine Delsaute -
Mardi 15 septembre 2026 à 17h00 - Salle Jean-Baptiste Carnoy (B.059) - Bâtiment Carnoy - Croix du Sud - 1348 Louvain-la-Neuve -
PRDX5 is a cytoprotective antioxidant enzyme with neuroprotective effects. In 2014, clinicians from Assistance Publique–Hôpitaux de Paris identified a homozygous nonsense mutation in PRDX5 (p.Gln121X), together with missense mutations in MARK2 (p.Arg445Trp) and NPAS4 (p.Thr587Met), in sisters with a neurodevelopmental syndrome. This thesis investigates the potential contribution of these variants. In silico analyses showed that, unlike PRDX5 p.Gln121X, the MARK2 and NPAS4 variants are reported in databases, although functional predictions are inconsistent. In fibroblasts from two patients, PRDX5 p.Gln121X transcripts were degraded by nonsense-mediated decay, while any transcripts escaping this pathway produced a truncated protein degraded by the proteasome. MARK2 mRNA levels were reduced, although this was not reflected at the protein level. NPAS4 expression could not be assessed in fibroblasts. To investigate the consequences of PRDX5 loss, SH-SY5Y PRDX5 KO cells were generated using CRISPR-Cas9. Following H₂O₂ exposure, KO cells showed increased resistance, reduced apoptosis and ROS production, and lower oxidative damage compared with controls. The results suggest that PRDX5 loss can be compensated for in SH-SY5Y cells, potentially through Nrf2 activation and subsequent upregulation of antioxidant defences. Recent clinical findings identified a homozygous variant in the non-coding RNU2-2 gene, now considered the most likely cause of the sisters’ neurodevelopmental syndrome. While this variant likely plays a major role, contributions from the PRDX5, MARK2 and NPAS4 variants cannot be excluded.
Jury members :
Prof. Melissa Page (UCLouvain) (Supervisor)
Prof. Bernard Knoops (UCLouvain) (Supervisor)
Prof. François Chaumont (UCLouvain) (Chairperson)
Prof. René Reszohazi (UCLouvain) (Secretary)
Prof. Emilie Decleves (UMons)
Prof. Xavier De Deken (ULB)
Pay attention : the public defense of Marine Delsaute will also take place in the form of a videoconference
