Targeted gene/syndrome under study
UBE2O (OMIM *617649, ubiquitin-conjucating enzyme E2 type O)
Abstract
We have seen a 14-years-old girl with mild ID, poor language function, epilepsy, gait ataxia, stagnation of skills after childhood and normal brain MRI where whole exome sequencing identified a de novo frameshift UBE2O variant predicting replacement of 152 C-terminal amino acids with 49 others. In vitro functional studies in transfected HEK293FT cells showed abolished auto-ubiquitination of UBE2O and reduced UBE2O protein level.
UBE2O is a hybrid E2/E3 ubiquitin ligase with high brain expression and low loss-of-function and missense tolerance.
We have established functional testing for UBE2O in our laboratory (site directed mutagenesis, cell line transfection, auto-ubiquitination and protein stability) and are interested in testing other variants as long as we also know the affected individual’s phenotype.
The Norwegian ERN-ITHACA is a network involved in the care and genetic investigation of individuals with rare or undiagnosed neurodevelopmental disorders located in 5 genetic centres across the country. We present possible novel NDD candidate genes in an effort to match our findings. Supported by the Norwegian rare disease fund grant #43066.
Coordinating clinicians/researchers
Sofia Douzgou Houge – sofia.douzgou.houge@helse-bergen.no
Prof Gunnar Douzgos Houge
Institution
Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway
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