Lafora disease is caused by mutations in either the EPM2A or EPM2B genes.
Understanding Lafora Disease Genes
Lafora disease is a rare, progressive form of epilepsy characterized by seizures, muscle spasms, difficulty coordinating movement (ataxia), and a decline in intellectual function. These symptoms typically appear during adolescence. The disease is caused by genetic mutations primarily in two genes:
- EPM2A: This gene encodes the protein laforin, which is a phosphatase.
- EPM2B (also called NHLRC1): This gene encodes the protein malin, which is a ubiquitin ligase.
Laforin and malin work together as a complex. Laforin is a phosphatase that binds to carbohydrates, and malin is an E3 ubiquitin ligase which targets misfolded or unneeded proteins for degradation.
Gene Function and Lafora Disease
Mutations in either EPM2A or EPM2B disrupt the normal function of the laforin-malin complex. This complex is essential for regulating glycogen metabolism within cells. When the complex is not functioning correctly, abnormally structured glycogen accumulates within cells, forming Lafora bodies. These Lafora bodies interfere with normal cell function, particularly in the brain and muscles, leading to the symptoms of Lafora disease.
Genes Implicated in Lafora Disease:
| Gene | Encoded Protein | Protein Function |
|---|---|---|
| EPM2A | Laforin | Phosphatase involved in glycogen metabolism |
| EPM2B (NHLRC1) | Malin | Ubiquitin ligase that works with laforin in glycogen metabolism regulation |
