Graph 2 shows the percentage distribution of the cases from either an EPM2A gene mutation or an EPM2B (NHLRC1) gene mutation. 42% of the cases are caused by EPM2A and 58% are caused by EPM2B (NHLRC1). The most common mutation on the EPM2A gene is the R241X mutation. This genetic mutation is the cause for 17% of the EPM2A caused Lafora Disease cases.EPM2A codes for the protein laforin, a dual-specificity phosphatase that acts on carbohydrates by taking phosphates off.NHLRC1 encodes the protein malin, an E3 ubiquitin ligase, that regulates the amount of laforin.Laforin is essential for making the normal structure of a glycogen molecule. When the mutation occurs on the EPM2A gene, laforin protein is down-regulated and less amount of this protein is present or none is made at all. If there is also a mutation in the NHLRC1 gene that makes the protein malin, then laforin cannot be regulated and thus less of it is made. Less Laforin means more phosphorylation of glycogen, causing conformational changes, rendering it insoluble, leading to an accumulation of misformed glycogen, which has neurotoxic effects.
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This article incorporates public domain text from The U.S. National Library of Medicine