Scientists Find Gene For Severe Form Of Epilepsy

"With approximately 40 million affected people worldwide, epilepsy is one of the most common neurological disorders," explains Scherer, a scientist in the Genetics and Genomic Biology program and the Centre for Applied Genomics at HSC and an Assistant Professor of Molecular and Medical Genetics at the U of T. "Lafora disease occurs during late childhood or early adolescence and is characterized by seizures and progressive neurological degeneration. Death usually occurs within a decade of the first symptoms."

While Lafora disease is rare in Canada, it is more common in Mediterranean countries and in Turkey, India and Iran.

Fifty years of investigation led biochemists to suspect that LD was caused by problems with carbohydrate metabolism in the brain. Beyond this, however, the fundamental defect triggering the malfunction was unknown. "Identifying the LD gene gives us the key to open the 'door' of the cell so we can determine the cause of the seizures," says Scherer.

The LD gene produces a signalling protein which is thought to be involved in the brain's breakdown of carbohydrates. The defective gene interferes with this process, leading to the accumulation of abnomal sugar molecules which likely lead to the destruction of the brain's nerve cells. Interestingly, accumulations of apparently the same composition are also found in normal aged brains with no obvious consequence.

"This discovery opens an entire new area of research into not only epilepsy but also normal brain function," says Dr. Berge Minassian, a neurologist at HSC and key scientist in the study. "While signalling molecules similar to the LD gene have been associated with forms of cancer, this is the first description of such a protein causing a neurological disease."

Identifying the LD gene will now enable scientists to develop accurate genetic diagnostic tools. "Ultimately, we hope that understanding the basic genetic defect will allow us to, not only discover the basic mechanisms that underly the severe epilepsy in this disorder, but also to correct the disease by gene therapy or other therapeutic treatments," explains Dr. Carter Snead, HSC's head of Neurology, Brain and Behaviour Research, holder of the Bloorview Childrens Hospital Chair in Paediatric Neuroscience, and Professor of Paediatrics and Medicine, U of T.

The Centre for Applied Genomics was established at The Hospital for Sick Children in July 1998 and conducts research focused on DNA sequencing and chromosome mapping, disease gene discovery, and bioinformatics.

This research was supported by grants from the Medical Research Council of Canada and The Hospital for Sick Children Foundation.