Spanish Researchers Shed Light on Rare Gene Deletions That Can Cause Angelman Syndrome

In rare cases, loss of part of the UBE3A gene can lead to Angelman syndrome, Spanish researchers report.

The team at the Autonomous University of Barcelona based their conclusion on a case study of two children with Angelman features. Their work added to the little knowledge there is about gene deletions causing some cases.

Since the deletions can be hard to spot, the team argued that they may be behind some of the Angelman cases that researchers have been unable to find genetic causes for.

Their study, published in the journal BMC Medical Genetics, is titled “Novel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: case report and review of the literature.”

The cause of Angelman syndrome is an UBE3A gene mutation that is most often inherited from a mother.

Fathers and mothers usually contribute a copy of each gene to a child. In most cases, the copies are equally active. But in parts of the brain, only the maternal copy of the UBE3A gene is active.

If the maternal copy has a mutation, or if a lot of the chromosome the gene sits in is missing, the child can develop Angelman syndrome. Faulty molecular processes that switch off the gene can also cause the condition. So can cases of both copies of the gene being inherited from the father.

The girls whom the Barcelona team studied had many Angelman features — a small head, intellectual disability, an inability to speak, movement problems and seizures. They also had attention problems and the typical happy demeanor of Angelman patients, with frequent smiling and laughing.

Researchers used gene analysis to discover that the girls lacked parts of their UBE3A genes. One had a deletion that eliminated a signal telling the gene’s protein-making machinery to start working. This prevented the brain from obtaining the protein.

In both girls, the loss of the genetic material appeared as mutations that had not been inherited from their mothers. Researchers noted that if a mother carries this mutation there is a 50 percent chance she will have another child with Angelman syndrome.

The team said previous studies have dealt with only seven cases of Angelman stemming from gene deletions — making it a very rare cause of the disease.

Not all gene analysis techniques can spot deletions, so the researchers argued that deletions may be behind more Angelman cases than experts realize.