Targeted gene(s)/phenotype under study :
- RAB10 (612672)
By trio-based exome sequencing, we identified a de novo missense variant in RAB10 gene p.Thr23Ile in a patient with microcephaly, corpus callosum agenesis, hypotonia, severe developmental delay, and epilepsy.
The variant was not present in Gnomad and was predicted to be deleterious by in-silico Additionally, RAB10 gene is significantly depleted of missense variants. RAB proteins are small GTPases that cycle between an active (GTP-bound) and inactive (GDP-bound) state. RAB proteins are involved in intracellular trafficking and synaptic function and mutations in RAB proteins (RAB18, RAB39B, RAB11B) have been associated with neurodevelopmental disorders. Interestingly, the missense p.Thr23Ile variant in RAB10 detected in our patient affects an highly conserved amino acid residue that is well known to affect GTP/GDP binding. Dominant-negative GDP-locked (p.Thr23Asn) RAB10 mutant indeed is known to result in abnormalities of the endoplasmic reticulum dynamics affecting dendritic growth.
Coordinating clinicians/researchers: Nicola Brunetti-Pierri
Federico II University
Department of Translational Medicine
Contact : email@example.com
Specific requirements beyond clinical data and genotype data sharing:
- Re-analysis of DNA samples : Y
- Resampling of patients : N
- Linked to a translational/basic research project? Y