Targeted gene(s)/phenotype under study



By trio-based exome sequencing, we identified a missense variant (c.2291C>T(p.Ser764Phe)) in the X-linked WDR44 gene, in a male patient with intellectual disability, mild microcephaly, structural brain anomalies, congenital heart defects, kidney cysts, cryptorchidism, musculoskeletal anomalies (talipes equinovarus, congenital hip dysplasia, increased CPK and joint hypermobility) and low platelet. Through collaborations, we have collected additional cases with similar phenotype, harbouring either missense or nonsense variants in WDR44.

WDR44, also known as Rabphillin11, is thought to be involved in endosomal and vesicle recycling through the interaction with a small G protein (Rab11p), a key regulators of intracellular membrane trafficking. Recently, WDR44 depletion has been shown to promote Rabin8 preciliary trafficking and ciliogenesis-initiating events at the mother centriole.

We have ongoing functional studies in patients-derived fibroblasts to show a possible ciliogenesis defect and assess the dynamic interaction with Rab11. Lastly, we aim to investigate the impact of the WDR44 variants in a zebrafish model.

These data likely support the evidence of a novel X-linked neurodevelopmental disorder linked to WDR44 variants. We look for other patients with WDR44 variants sharing similar clinical features.

Coordinating clinicians/researchers

Andrea Accogli

Valeria Capra


Medical Genetics, Instituto G.Gaslini,
Instituto G.Gaslini

Specific requirements beyond clinical data and genotype data sharing

  • Re-analysis of DNA samples : No
  • Resampling of patients : No
  • Linked to a translational/basic research project: Yes