What causes UBE3B-related disorder at the molecular level?
The UBE3Bgene gives the instructions for making a protein that helps tag other proteins inside cells so they can be broken down or moved to the right place at the right time, a process that is especially active while the brain and face are developing before birth. When both copies of the UBE3Bgene are changed, this protein does not work properly, leading to the features of this condition.
What type of genetic change causes this condition?
UBE3B-related disorder is caused by many different types of gene changes, and different families often carry their own unique change. That said, researchers have found that several unrelated Egyptian families share the same specific gene change, called c.1076G>A (p.W359*). Because these families come from the same part of Upper Egypt and do not appear to be closely related to one another, this change is thought to be a “founder variant” (meaning it likely originated in a shared ancestor many generations ago and has since been passed down independently within that region). Identifying this variant can help guide and speed up genetic diagnosis for families from this part of Egypt who have a child with features suggestive of this condition.
How is the diagnosis made?
The diagnosis is suspected based on the characteristic combination of facial features, developmental delay, and brain scan findings, and confirmed through genetic testing of the UBE3Bgene. Once a gene change is confirmed in an affected child, both parents should be tested to confirm they are carriers.
UBE3B