Source of infantile epilepsy found in a gene

By Dr. Ananya Mandal, MDJan 16 2012

Researchers from Adelaide have discovered a 20-year mystery about a type of epilepsy in infants. It is caused by a single mutation in one gene they found. The discovery will allow for better screening, diagnosis and prediction of the risk of seizures for sufferers of benign familial infantile epilepsy, the researchers say.

University of South Australia research fellow Dr Susan Heron said yesterday the rare condition occurred in about 60 Australian families. She said the mutation was pinned to the chromosome responsible more than 15 years ago but the particular gene had been hard to identify. “It was difficult to find because it wasn't a gene that you would think about linking to epilepsy,” Dr Heron said. “The gene that we found is not a type of gene that's been known to be involved with epilepsy before.”

The mutation causing the disorder adds one more code to a 12-code sequence on chromosome 16, which affects a gene known as PRRT2. Of 23 families previously diagnosed with benign familial infantile epilepsy, DNA analysis found the mutation present in 19 families.

Dr Heron said children with the condition typically suffered seizures from the age of six months to two years. Later in life, the genetic mutation can cause a movement disorder, characterized by sudden, startling, involuntary jerks when the children start moving. “The children grow out of epilepsy but they can develop a movement disorder,” Dr Heron said. She said families would now be able to have their children screened for the mutation, with a definite diagnosis made. “If we can confirm what they have, we can better target treatment,” she said.

Professor Ingrid Scheffer, from the Melbourne team began looking at the disorder some 20 years ago. She said it was already known the gene made a protein called proline rich transmembrane protein 2. “That means we can home in on what's happening biochemically and start to develop targeted treatments for the condition,” she said.

The study of 23 families from Australia, New Zealand and Israel, some of which Prof Scheffer has tracked for 20 years, 19 families had a mutation of the gene and 15 families had the same mutation. “We call that a mutation hot spot,” Prof Sheffer told AAP. “It shows that that gene is likely to become abnormal at this one position. The gene was found a couple of months ago by a Chinese group in families with the movement disorder. What we found is that the same gene and in fact the same mutation, the same abnormality, is now a cause of infantile epilepsy.” Prof Scheffer said an estimated 60 Australian families have the abnormal gene.

The UniSA researchers made the discovery in conjunction with a team at the University of Melbourne. The work was published on Friday in the American Journal of Human Genetics.