EPM2A

The EPM2A gene provides instructions for making a protein called laforin. Although this protein is active in cells throughout the body, it appears to play a critical role in the survival of nerve cells (neurons) in the brain.

Studies suggest that laforin has multiple functions within cells. To carry out these functions, laforin interacts with several other proteins, including malin (which is produced from the NHLRC1 gene). These proteins are part of complex networks that transmit chemical signals and break down unneeded or abnormal proteins. Additionally, laforin may act as a tumor suppressor protein, which means that it keeps cells from growing and dividing in an uncontrolled way.

Laforin and malin likely play a critical role in regulating the production of a complex sugar called glycogen. Glycogen is a major source of stored energy in the body. The body stores this sugar in the liver and muscles, breaking it down when it is needed for fuel. Researchers believe that laforin and malin may prevent a potentially damaging buildup of glycogen in tissues that do not normally store this molecule, such as those of the nervous system.

Lafora progressive myoclonus epilepsy - caused by mutations in the EPM2A gene

More than 50 mutations in the EPM2A gene have been identified in people with Lafora progressive myoclonus epilepsy. Many of these mutations change single protein building blocks (amino acids) in the laforin protein. Other mutations delete or insert genetic material in the EPM2A gene. Almost all mutations in this gene prevent cells from producing any laforin or lead to the production of a nonfunctional version of the protein.

It is unclear how mutations in the EPM2A gene lead to the major features of Lafora progressive myoclonus epilepsy. Studies suggest that a loss of laforin prevents cells from regulating the production of glycogen. As a result, distinctive clumps called Lafora bodies form within many types of cells. Lafora bodies are made up of an abnormal form of glycogen (called polyglucosan) that cannot be broken down and used for fuel. Instead, polyglucosans build up to form clumps that can damage cells. Neurons appear to be particularly vulnerable to this type of damage. Although Lafora bodies are found in many of the body's tissues, the signs and symptoms of Lafora progressive myoclonus epilepsy are limited to the nervous system.

Researchers are uncertain how a loss of functional laforin contributes to the formation of Lafora bodies. However, a lack of this protein ultimately results in the death of neurons, which interferes with the brain's normal functions. The degeneration of neurons likely underlies the seizures, movement abnormalities, intellectual decline, and other neurological problems seen with Lafora progressive myoclonus epilepsy.